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1
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Ashish S, Raj MS, Monga D, Finley G. Rechallenging Fluoropyrimidine-Induced Cardiotoxicity and Neurotoxicity: A Report of Two Cases. Cureus 2022; 14:e26824. [PMID: 35971344 PMCID: PMC9372383 DOI: 10.7759/cureus.26824] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/13/2022] [Indexed: 11/22/2022] Open
Abstract
Fluoropyrimidines (FP's) such as fluorouracil (5-FU) and capecitabine are antimetabolites widely used in many solid tumors. FPs side effects are caused mainly by a lack of dihydropyrimidine dehydrogenase (DPD) enzyme. It has been noticed that treatment with infusional regimens of 5-FU is associated with more adverse events (AE) compared to bolus forms. Here, we report two cases of unusual side effects seen with infusional 5-FU and capecitabine and how early intervention by withholding ongoing treatment can help in preventing progression and mortality.
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Affiliation(s)
- Sethi Ashish
- Department of Hematology and Oncology, Allegheny Health Network, Pittsburgh, USA
| | - Moses S Raj
- Department of Hematology and Oncology, Allegheny Health Network, Pittsburgh, USA
| | - Dulabh Monga
- Department of Hematology and Oncology, Allegheny Health Network, Pittsburgh, USA
| | - Gene Finley
- Department of Hematology and Oncology, Allegheny Health Network, Pittsburgh, USA
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2
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Guven DC, Yalcin S. Neoadjuvant capecitabine in rectal cancer chemoradiotherapy: too early to ring the alarms. Intern Med J 2021; 51:1365-1366. [PMID: 34423543 DOI: 10.1111/imj.15321] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Accepted: 02/19/2021] [Indexed: 02/05/2023]
Affiliation(s)
- Deniz Can Guven
- Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Turkey
| | - Suayib Yalcin
- Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Turkey
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Abstract
The conventional treatment for cT3-T4 or node-positive clinically resectable rectal cancer is long course preoperative chemoradiation followed by surgery and postoperative adjuvant chemotherapy. Disadvantages of this approach include possible overtreatment of patients, 6 weeks of daily radiation treatment, and undetected metastatic disease. There are a number of emerging trends which are changing this approach to treatment. Selected topics included in this manuscript include the selective use of pelvic radiation, the role of radiation for a positive radial margin, the interval between radiation and surgery, non-operative management, new chemoradiation regimens, short vs. long course radiation, and the role of postoperative adjuvant chemotherapy.
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Affiliation(s)
- Bruce D. Minsky
- Department of Radiation Oncology, MD Anderson Cancer Center, Houston, TX, USA
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4
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Shoji H, Motegi M, Osawa K, Asao T, Kuwano H, Takahashi T, Ogoshi K. The first thermic treatment predicts following chemoradiation response with concurrent thermal therapy for the treatment of rectal cancer. Oncol Lett 2018; 16:497-504. [PMID: 29928438 DOI: 10.3892/ol.2018.8630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2018] [Accepted: 04/26/2018] [Indexed: 11/05/2022] Open
Abstract
The present study aimed to evaluate whether the neoadjuvant chemoradiation response with concurrent thermal therapy for the treatment of rectal cancer can be predicted following the first thermic treatment. Eighty patients with primary rectal adenocarcinoma (≤12 cm from the anal verge) were included in this study. Fifty-four received surgery and pathological response was evaluated. Intensity-modulated radiotherapy was administered conventionally once daily 5 times/week. Neoadjuvant radiotherapy consisted of 50 Gy delivered to the planning target volume in 25 fractions. Concurrent neoadjuvant chemotherapy was delivered in 5-day courses. Capecitabine was administered orally at 1,700 mg/m2/day for 5 days/week. Thermic treatment was performed using the Thermotron-RF 8 and administered once/week for 5 weeks with 50 min irradiation. Patients with a gross tumor volume (GTV) ≤32 cm3 and a radiofrequency (RF) output difference (RO difference) ≥77 Watt/min exhibited pathological complete response (pCR) and CR rates of 50 and 75%, respectively. Those with a GTV ≥80 cm3 and a RO difference ≥77 Watt/min exhibited pCR and CR rates of 42.9 and 42.9%, respectively. The changes in the skin temperature during RF treatment in patients with pCR with a RO difference ≥77 Watt/min increased significantly compared with those of other outcomes, and progressive disease. These data suggest a strategy for predicting which patients will respond best following the first thermic treatment. The results identified that the group of patients with a GTV ≤32 cm3 and a RO difference ≥77 Watt/min (outputable/heatable patients) may respond best.
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Affiliation(s)
- Hisanori Shoji
- Division of Surgery, Hidaka Hospital, Takasaki, Gunma 370-0001, Japan
| | - Masahiko Motegi
- Division of Surgery, Hidaka Hospital, Takasaki, Gunma 370-0001, Japan
| | - Kiyotaka Osawa
- Division of Surgery, Hidaka Hospital, Takasaki, Gunma 370-0001, Japan
| | - Takayuki Asao
- Initiative for Advanced Research, Gunma University, Maebashi, Gunma 371-8511, Japan
| | - Hiroyuki Kuwano
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma 371-8511, Japan
| | - Takeo Takahashi
- Department of Radiation Oncology, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama 350-8550, Japan
| | - Kyoji Ogoshi
- Division of Cancer Diagnosis and Cancer Treatment, Hidaka Hospital, Takasaki, Gunma 370-0001, Japan
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5
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Yoon WS, Park W, Choi DH, Ahn YC, Chun HK, Lee WY, Yun SH, Kang WK, Lim HY, Park YS. Importance of the Circumferential Extent of Tumors and Clinical Lymph Node Status as Prognostic Factors after Preoperative Chemoradiotherapy and Surgery in Patients with Rectal Cancer. TUMORI JOURNAL 2018; 96:568-76. [DOI: 10.1177/030089161009600409] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Aims and background To evaluate the clinical factors that influence pathological and clinical outcomes after preoperative concurrent chemoradiotherapy in patients with rectal cancer. Methods Between 1999 and 2004, 121 patients with cT3-4 or node-positive rectal cancer received preoperative chemoradiotherapy and surgery. Preoperative radiation therapy with 45 Gy was delivered. Fluorouracil-based chemotherapy was administered to most of the patients. Results Pathological complete remission was 14.3% after preoperative chemoradiotherapy. More than 60% tumor circumferential extent was an independent adverse factor for complete remission (P = 0.011, HR 4.643, 95% CI 1.415–15.231). Local recurrence developed in 9.9% of the cases. Serum CEA level ≥5 ng/ml (P = 0.057, HR 3.022, 95% CI 0.967–9.441) and >60% circumferential extent of tumor (P = 0.064, HR 4.232, 95% CI 0.918–19.531) were marginal adverse factors for local recurrence. Five-year disease-free survival and overall survival were 72.2% and 86.6%, respectively. Disease-free survival was poor for patients with the lymph nodes ≥1 cm in diameter (P = 0.028), cN2 stage disease (P = 0.047) and >60% circumferential extent of tumor (P = 0.058). Multivariate analysis for disease-free survival showed that the lymph node size ≥1 cm was an adverse factor (P = 0.019, HR 2.380, 95% CI 1.115–4.906). Patients with >60% circumferential extent of tumor and cN2 stage had a more unfavorable survival than the other patients (disease-free survival, P = 0.018; overall survival, P = 0.015). Patients with >60% circumferential extent of tumor and/or lymph node ≥1 cm also had an unfavorable survival (disease-free survival, P = 0.016; overall survival, P = 0.049). Conclusions In rectal cancer, circumferential extent of tumor and clinical lymph node status were important factors for preoperative chemoradiotherapy and surgery. A further prospective study is needed to confirm and expand these findings.
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Affiliation(s)
- Won Sup Yoon
- Department of Radiation Oncology, Korea University Medical Center, Korea University College of Medicine, Seoul, Republic of Korea
| | - Won Park
- Departments of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Doo Ho Choi
- Departments of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Yong Chan Ahn
- Departments of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Ho Kyung Chun
- Departments of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Woo Yong Lee
- Departments of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Seong Hyeon Yun
- Departments of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Won Ki Kang
- Departments of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Ho Yeong Lim
- Departments of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Young Suk Park
- Departments of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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6
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Minsky BD. Neoadjuvant Treatment Strategies: Advanced Radiation Alternatives. Clin Colon Rectal Surg 2017; 30:377-382. [PMID: 29184473 PMCID: PMC5703672 DOI: 10.1055/s-0037-1606115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Long-course chemoradiation therapy (CRT) has been the standard approach for locally advanced rectal tumors. Neoadjuvant CRT is associated to improved local disease control, with less toxicity when compared with adjuvant CRT, as well as the chance for pathologic complete response. The CRT regimens have improved over the past years. This article will examine selected controversies, including novel chemoradiation regimens, duration of radiation (short vs. long course), and radiation techniques such as intensity-modulated radiation therapy (IMRT).
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Affiliation(s)
- Bruce D. Minsky
- Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas
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7
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Jootun N, Evans T, Mak J, Makin G, Platell C. Comparing pathological complete response rate using oral capecitabine versus infusional 5-fluorouracil with preoperative radiotherapy in rectal cancer treatment. ANZ J Surg 2017; 88:62-65. [DOI: 10.1111/ans.14192] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2017] [Revised: 06/28/2017] [Accepted: 07/16/2017] [Indexed: 12/27/2022]
Affiliation(s)
- Narotam Jootun
- Department of Surgery; Fiona Stanley Hospital; Perth Western Australia Australia
| | - Tess Evans
- Department of Surgery; Fiona Stanley Hospital; Perth Western Australia Australia
| | - Jackie Mak
- Department of Surgery; Fiona Stanley Hospital; Perth Western Australia Australia
| | - Greg Makin
- Department of Surgery; Fiona Stanley Hospital; Perth Western Australia Australia
| | - Cameron Platell
- Department of Colorectal Cancer Unit; St John of God Hospital; Perth Western Australia Australia
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8
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Zou XC, Wang QW, Zhang JM. Comparison of 5-FU-based and Capecitabine-based Neoadjuvant Chemoradiotherapy in Patients With Rectal Cancer: A Meta-analysis. Clin Colorectal Cancer 2017; 16:e123-e139. [PMID: 28284574 DOI: 10.1016/j.clcc.2017.01.009] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2016] [Revised: 11/17/2016] [Accepted: 01/13/2017] [Indexed: 12/27/2022]
Abstract
INTRODUCTION The inconvenience of using infusion therapies resulted in the development of capecitabine (CA), an oral fluoropyrimidine. In this meta-analysis, we evaluated 10 studies that compared the efficacy and safety of an oral CA-based regimen with those of a continuous infusion 5-fluorouracil (5-FU) regimen for neoadjuvant chemoradiotherapy in patients with rectal cancer. MATERIALS AND METHODS The databases searched included Medline, Cochrane, EMBASE, and Google Scholar (until August 31, 2016). The primary outcome assessed was the rate of postoperative down-staging of the tumor and pathologic complete response. The secondary outcomes were disease-free survival (DFS) and overall survival (OS). RESULTS This meta-analysis (5 retrospective studies, 3 prospective studies, and 2 randomized controlled trials [RCTs]) compared the efficacy of the 5-FU arm (n = 757) to that of the CA arm (n = 719). There was no significant difference in tumor down-staging rate between the 2 regimens (RCTs/prospective studies: odds ratio [OR], 0.88; 95% confidence interval [CI], 0.65-1.20; P = .416; retrospective studies: OR, 0.84; 95% CI, 0.50-1.44; P = .534). There was also no significant difference in pathologic complete response (RCTs/prospective studies: OR, 0.80; 95% CI, 0.52-1.23; P = .304; retrospective studies: OR, 0.73; 95% CI, 0.48-1.12; P = .149), or survival rates (3-year, 5-year DFS, and 5-year OS rate) between the 2 groups. The CA group had a higher number of patients reporting diarrhea and hand-foot syndrome compared with the 5-FU group. The 5-FU group had a higher number of patients reporting mucositis compared with the CA group. CONCLUSIONS Our data suggested that oral CA was equivalent to continuous infusion 5-FU in the curative setting of rectal cancer during neoadjuvant chemoradiotherapy.
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Affiliation(s)
- Xiang-Cai Zou
- Department of Gastrointestinal Surgery, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Qi-Wen Wang
- Laboratory of Surgery, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Ji-Min Zhang
- Department of Gastrointestinal Surgery, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
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9
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Shoji H, Motegi M, Takakusagi Y, Asao T, Kuwano H, Takahashi T, Ogoshi K. Chemoradiotherapy and concurrent radiofrequency thermal therapy to treat primary rectal cancer and prediction of treatment responses. Oncol Rep 2016; 37:695-704. [PMID: 27959450 PMCID: PMC5355662 DOI: 10.3892/or.2016.5300] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2016] [Accepted: 08/10/2016] [Indexed: 12/18/2022] Open
Abstract
The present study aimed to evaluate a previously reported predictive formula of output-limiting symptoms induced by radiofrequency (RF) to determine the efficacy of this neoadjuvant chemoradiation (NACR) and concurrent RF thermal therapy. The present study included 81 consecutive patients with confirmed diagnoses of rectal adenocarcinoma that was localized in the mid-low rectum (up to 12 cm from the anal verge) who received NACR [intensity-modulated radiotherapy (IMRT), 50 Gy/25 fractions, capecitabine 1,700 mg/m2/day for 5 days/week)] with concurrent thermal therapy (Thermotron-RF8, once a week for 5 weeks with 50 min irradiation). Patients with progressive disease (PD) did not receive RF outputs higher than the predicted value. Some patients who were predicted to receive more output in fact received more than the predicted output. In patients who were predicted to receive moderately higher outputs, 37.5% of the patients experienced pathological complete responses, which was the highest rate, while in those who did not receive more than the predicted output, 66.7% of the patients experienced PD, which was the highest rate in the present study. We speculate that RF thermal therapy may offset the chemoradiation effects in some patients. Adding thermal therapy as a multimodality therapy to NACR potentially affects patients with lower predicted outputs and actual observed outputs slightly higher than the predictive value. Our predictive equation for initial energy output, in which output‑limiting symptoms can be used to predict treatment efficacy, consequently, can be used to decide whether to continue this treatment modality.
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Affiliation(s)
- Hisanori Shoji
- Division of Surgery, Hidaka Hospital, Gunma 370-0001, Japan
| | | | | | - Takayuki Asao
- Initiative for Advanced Research, Gunma University, Gunma 371-8511, Japan
| | - Hiroyuki Kuwano
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Gunma 371-8511, Japan
| | - Takeo Takahashi
- Department of Radiation Oncology, Saitama Medical Center, Saitama Medical University, Saitama 350-8550, Japan
| | - Kyoji Ogoshi
- Division of Cancer Diagnosis and Cancer Treatment, Hidaka Hospital, Gunma 370-0001, Japan
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10
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Effect of Neoadjuvant Chemoradiotherapy with Capecitabine versus Fluorouracil for Locally Advanced Rectal Cancer: A Meta-Analysis. Gastroenterol Res Pract 2016; 2016:1798285. [PMID: 27891147 PMCID: PMC5116508 DOI: 10.1155/2016/1798285] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2016] [Accepted: 06/30/2016] [Indexed: 11/17/2022] Open
Abstract
A meta-analysis was carried out to compare the efficacy and safety of capecitabine plus radiation with 5-fluorouracil (5-FU) plus radiotherapy (RT) as neoadjuvant treatment in locally advanced rectal cancer (LARC). We searched the Cochrane database, Ovid, Medline, Embase, ISI databases, and Chinese Biomedical Literature Database between January 1998 and October 2014. Trials of capecitabine compared with 5-FU plus RT as neoadjuvant treatment for LARC were considered for inclusion. RevMan software was used to analyze these data. Nine trials were included in this meta-analysis, which covered a total of 3141 patients. The meta-analysis showed that capecitabine group had statistically significant better pCR rates (OR, 1.34; 95% CI, 1.10-1.64; P = 0.003), T downstaging rates (OR, 1.58; 95% CI, 1.22-2.06; P = 0.0007), N downstaging rates (OR, 2.06; 95% CI, 1.34-3.16; P = 0.001), less distant metastasis (OR, 0.63; 95% CI, 0.44-0.88; P = 0.007), and lowered leucocytes (OR, 0.25; 95% CI, 0.11-0.54; P = 0.0005), but with higher incidence of hand-foot syndrome (HFS) (OR, 4.43; 95% CI, 1.59-12.33; P = 0.004). Capecitabine was more efficient than 5-FU in terms of tumor response in neoadjuvant treatment for patients with LARC and favourably low toxicity with the exception of HFS.
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11
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Milinis K, Thornton M, Montazeri A, Rooney PS. Adjuvant chemotherapy for rectal cancer: Is it needed? World J Clin Oncol 2015; 6:225-236. [PMID: 26677436 PMCID: PMC4675908 DOI: 10.5306/wjco.v6.i6.225] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2015] [Revised: 08/01/2015] [Accepted: 09/08/2015] [Indexed: 02/06/2023] Open
Abstract
Adjuvant chemotherapy has become a standard treatment of advanced rectal cancer in the West. The benefits of adjuvant chemotherapy after surgery alone have been well established. However, controversy surrounds the use adjuvant chemotherapy in patients who received preoperative chemoradiotherapy, despite it being recommended by a number of international guidelines. Results of recent multicentre randomised control trials showed no benefit of adjuvant chemotherapy in terms of survival and rates of distant metastases. However, concerns exist regarding the quality of the studies including inadequate staging modalities, out-dated chemotherapeutic regimens and surgical approaches and small sample sizes. It has become evident that not all the patients respond to adjuvant chemotherapy and more personalised approach should be employed when considering the benefits of adjuvant chemotherapy. The present review discusses the strengths and weaknesses of the current evidence-base and suggests improvements for future studies.
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12
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Allegra CJ, Yothers G, O'Connell MJ, Beart RW, Wozniak TF, Pitot HC, Shields AF, Landry JC, Ryan DP, Arora A, Evans LS, Bahary N, Soori G, Eakle JF, Robertson JM, Moore DF, Mullane MR, Marchello BT, Ward PJ, Sharif S, Roh MS, Wolmark N. Neoadjuvant 5-FU or Capecitabine Plus Radiation With or Without Oxaliplatin in Rectal Cancer Patients: A Phase III Randomized Clinical Trial. J Natl Cancer Inst 2015; 107:djv248. [PMID: 26374429 DOI: 10.1093/jnci/djv248] [Citation(s) in RCA: 220] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2015] [Accepted: 08/05/2015] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND National Surgical Adjuvant Breast and Bowel Project R-04 was designed to determine whether the oral fluoropyrimidine capecitabine could be substituted for continuous infusion 5-FU in the curative setting of stage II/III rectal cancer during neoadjuvant radiation therapy and whether the addition of oxaliplatin could further enhance the activity of fluoropyrimidine-sensitized radiation. METHODS Patients with clinical stage II or III rectal cancer undergoing preoperative radiation were randomly assigned to one of four chemotherapy regimens in a 2x2 design: CVI 5-FU or oral capecitabine with or without oxaliplatin. The primary endpoint was local-regional tumor control. Time-to-event endpoint distributions were estimated using the Kaplan-Meier method. Hazard ratios were estimated from Cox proportional hazard models. All statistical tests were two-sided. RESULTS Among 1608 randomized patients there were no statistically significant differences between regimens using 5-FU vs capecitabine in three-year local-regional tumor event rates (11.2% vs 11.8%), 5-year DFS (66.4% vs 67.7%), or 5-year OS (79.9% vs 80.8%); or for oxaliplatin vs no oxaliplatin for the three endpoints of local-regional events, DFS, and OS (11.2% vs 12.1%, 69.2% vs 64.2%, and 81.3% vs 79.0%). The addition of oxaliplatin was associated with statistically significantly more overall and grade 3-4 diarrhea (P < .0001). Three-year rates of local-regional recurrence among patients who underwent R0 resection ranged from 3.1 to 5.1% depending on the study arm. CONCLUSIONS Continuous infusion 5-FU produced outcomes for local-regional control, DFS, and OS similar to those obtained with oral capecitabine combined with radiation. This study establishes capecitabine as a standard of care in the pre-operative rectal setting. Oxaliplatin did not improve the local-regional failure rate, DFS, or OS for any patient risk group but did add considerable toxicity.
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Affiliation(s)
- Carmen J Allegra
- NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA (CJA, GY, MJO, RWB, TFW, HCP, AFS, JCL, DPR, AA, LSE, NB, GS, JFE, JMR, DFMJr, MRM, BTM, PJW, SS, MSR, NW); Department of Medicine, University of Florida Health, Gainesville, FL (CJA); NRG Oncology and the University of Pittsburgh Graduate School of Public Health, Department of Biostatistics, Pittsburgh, PA (GY); Glendale Memorial Hospital, Glendale, CA (RWB); CCOP Christiana Care Health Systems, Newark, DE (TFW); Mayo Clinic, Rochester, MN and the ALLIANCE, Boston, MA (HCP); Wayne State University, Karmanos Cancer Institute, Detroit, MI and SWOG, San Antonio, TX (AFS); Emory University, Department of Radiation Oncology, Atlanta, GA and ECOG/ACRIN, Rochester, MN (JCL); Massachusetts General Hospital Cancer Center and the ALLIANCE, Boston, MA (DPR); Kaiser Permanente, Fremont, CA (AA); Novant Health Forsyth Medical Center, Winston-Salem, NC (LSE); University of Pittsburgh, Pittsburgh, PA (NB); Missouri Valley Cancer Consortium CCOP, Omaha, NE (GS); Florida Cancer Specialists, Fort Myers, FL (JFE); Beaumont Hospital System, Royal Oak, MI (JMR); Cancer Center of Kansas, Wichita, KS (DFMJr); Stroger Hospital Chicago MU-NCORP, Chicago, IL (MRM); Montana Cancer Consortium, Billings, MT (BTM); Oncology and Hematology Care, Cincinnati, OH (PJW); UF Health Cancer Center, Orlando FL (MSR); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (NW).
| | - Greg Yothers
- NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA (CJA, GY, MJO, RWB, TFW, HCP, AFS, JCL, DPR, AA, LSE, NB, GS, JFE, JMR, DFMJr, MRM, BTM, PJW, SS, MSR, NW); Department of Medicine, University of Florida Health, Gainesville, FL (CJA); NRG Oncology and the University of Pittsburgh Graduate School of Public Health, Department of Biostatistics, Pittsburgh, PA (GY); Glendale Memorial Hospital, Glendale, CA (RWB); CCOP Christiana Care Health Systems, Newark, DE (TFW); Mayo Clinic, Rochester, MN and the ALLIANCE, Boston, MA (HCP); Wayne State University, Karmanos Cancer Institute, Detroit, MI and SWOG, San Antonio, TX (AFS); Emory University, Department of Radiation Oncology, Atlanta, GA and ECOG/ACRIN, Rochester, MN (JCL); Massachusetts General Hospital Cancer Center and the ALLIANCE, Boston, MA (DPR); Kaiser Permanente, Fremont, CA (AA); Novant Health Forsyth Medical Center, Winston-Salem, NC (LSE); University of Pittsburgh, Pittsburgh, PA (NB); Missouri Valley Cancer Consortium CCOP, Omaha, NE (GS); Florida Cancer Specialists, Fort Myers, FL (JFE); Beaumont Hospital System, Royal Oak, MI (JMR); Cancer Center of Kansas, Wichita, KS (DFMJr); Stroger Hospital Chicago MU-NCORP, Chicago, IL (MRM); Montana Cancer Consortium, Billings, MT (BTM); Oncology and Hematology Care, Cincinnati, OH (PJW); UF Health Cancer Center, Orlando FL (MSR); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (NW)
| | - Michael J O'Connell
- NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA (CJA, GY, MJO, RWB, TFW, HCP, AFS, JCL, DPR, AA, LSE, NB, GS, JFE, JMR, DFMJr, MRM, BTM, PJW, SS, MSR, NW); Department of Medicine, University of Florida Health, Gainesville, FL (CJA); NRG Oncology and the University of Pittsburgh Graduate School of Public Health, Department of Biostatistics, Pittsburgh, PA (GY); Glendale Memorial Hospital, Glendale, CA (RWB); CCOP Christiana Care Health Systems, Newark, DE (TFW); Mayo Clinic, Rochester, MN and the ALLIANCE, Boston, MA (HCP); Wayne State University, Karmanos Cancer Institute, Detroit, MI and SWOG, San Antonio, TX (AFS); Emory University, Department of Radiation Oncology, Atlanta, GA and ECOG/ACRIN, Rochester, MN (JCL); Massachusetts General Hospital Cancer Center and the ALLIANCE, Boston, MA (DPR); Kaiser Permanente, Fremont, CA (AA); Novant Health Forsyth Medical Center, Winston-Salem, NC (LSE); University of Pittsburgh, Pittsburgh, PA (NB); Missouri Valley Cancer Consortium CCOP, Omaha, NE (GS); Florida Cancer Specialists, Fort Myers, FL (JFE); Beaumont Hospital System, Royal Oak, MI (JMR); Cancer Center of Kansas, Wichita, KS (DFMJr); Stroger Hospital Chicago MU-NCORP, Chicago, IL (MRM); Montana Cancer Consortium, Billings, MT (BTM); Oncology and Hematology Care, Cincinnati, OH (PJW); UF Health Cancer Center, Orlando FL (MSR); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (NW)
| | - Robert W Beart
- NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA (CJA, GY, MJO, RWB, TFW, HCP, AFS, JCL, DPR, AA, LSE, NB, GS, JFE, JMR, DFMJr, MRM, BTM, PJW, SS, MSR, NW); Department of Medicine, University of Florida Health, Gainesville, FL (CJA); NRG Oncology and the University of Pittsburgh Graduate School of Public Health, Department of Biostatistics, Pittsburgh, PA (GY); Glendale Memorial Hospital, Glendale, CA (RWB); CCOP Christiana Care Health Systems, Newark, DE (TFW); Mayo Clinic, Rochester, MN and the ALLIANCE, Boston, MA (HCP); Wayne State University, Karmanos Cancer Institute, Detroit, MI and SWOG, San Antonio, TX (AFS); Emory University, Department of Radiation Oncology, Atlanta, GA and ECOG/ACRIN, Rochester, MN (JCL); Massachusetts General Hospital Cancer Center and the ALLIANCE, Boston, MA (DPR); Kaiser Permanente, Fremont, CA (AA); Novant Health Forsyth Medical Center, Winston-Salem, NC (LSE); University of Pittsburgh, Pittsburgh, PA (NB); Missouri Valley Cancer Consortium CCOP, Omaha, NE (GS); Florida Cancer Specialists, Fort Myers, FL (JFE); Beaumont Hospital System, Royal Oak, MI (JMR); Cancer Center of Kansas, Wichita, KS (DFMJr); Stroger Hospital Chicago MU-NCORP, Chicago, IL (MRM); Montana Cancer Consortium, Billings, MT (BTM); Oncology and Hematology Care, Cincinnati, OH (PJW); UF Health Cancer Center, Orlando FL (MSR); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (NW)
| | - Timothy F Wozniak
- NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA (CJA, GY, MJO, RWB, TFW, HCP, AFS, JCL, DPR, AA, LSE, NB, GS, JFE, JMR, DFMJr, MRM, BTM, PJW, SS, MSR, NW); Department of Medicine, University of Florida Health, Gainesville, FL (CJA); NRG Oncology and the University of Pittsburgh Graduate School of Public Health, Department of Biostatistics, Pittsburgh, PA (GY); Glendale Memorial Hospital, Glendale, CA (RWB); CCOP Christiana Care Health Systems, Newark, DE (TFW); Mayo Clinic, Rochester, MN and the ALLIANCE, Boston, MA (HCP); Wayne State University, Karmanos Cancer Institute, Detroit, MI and SWOG, San Antonio, TX (AFS); Emory University, Department of Radiation Oncology, Atlanta, GA and ECOG/ACRIN, Rochester, MN (JCL); Massachusetts General Hospital Cancer Center and the ALLIANCE, Boston, MA (DPR); Kaiser Permanente, Fremont, CA (AA); Novant Health Forsyth Medical Center, Winston-Salem, NC (LSE); University of Pittsburgh, Pittsburgh, PA (NB); Missouri Valley Cancer Consortium CCOP, Omaha, NE (GS); Florida Cancer Specialists, Fort Myers, FL (JFE); Beaumont Hospital System, Royal Oak, MI (JMR); Cancer Center of Kansas, Wichita, KS (DFMJr); Stroger Hospital Chicago MU-NCORP, Chicago, IL (MRM); Montana Cancer Consortium, Billings, MT (BTM); Oncology and Hematology Care, Cincinnati, OH (PJW); UF Health Cancer Center, Orlando FL (MSR); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (NW)
| | - Henry C Pitot
- NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA (CJA, GY, MJO, RWB, TFW, HCP, AFS, JCL, DPR, AA, LSE, NB, GS, JFE, JMR, DFMJr, MRM, BTM, PJW, SS, MSR, NW); Department of Medicine, University of Florida Health, Gainesville, FL (CJA); NRG Oncology and the University of Pittsburgh Graduate School of Public Health, Department of Biostatistics, Pittsburgh, PA (GY); Glendale Memorial Hospital, Glendale, CA (RWB); CCOP Christiana Care Health Systems, Newark, DE (TFW); Mayo Clinic, Rochester, MN and the ALLIANCE, Boston, MA (HCP); Wayne State University, Karmanos Cancer Institute, Detroit, MI and SWOG, San Antonio, TX (AFS); Emory University, Department of Radiation Oncology, Atlanta, GA and ECOG/ACRIN, Rochester, MN (JCL); Massachusetts General Hospital Cancer Center and the ALLIANCE, Boston, MA (DPR); Kaiser Permanente, Fremont, CA (AA); Novant Health Forsyth Medical Center, Winston-Salem, NC (LSE); University of Pittsburgh, Pittsburgh, PA (NB); Missouri Valley Cancer Consortium CCOP, Omaha, NE (GS); Florida Cancer Specialists, Fort Myers, FL (JFE); Beaumont Hospital System, Royal Oak, MI (JMR); Cancer Center of Kansas, Wichita, KS (DFMJr); Stroger Hospital Chicago MU-NCORP, Chicago, IL (MRM); Montana Cancer Consortium, Billings, MT (BTM); Oncology and Hematology Care, Cincinnati, OH (PJW); UF Health Cancer Center, Orlando FL (MSR); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (NW)
| | - Anthony F Shields
- NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA (CJA, GY, MJO, RWB, TFW, HCP, AFS, JCL, DPR, AA, LSE, NB, GS, JFE, JMR, DFMJr, MRM, BTM, PJW, SS, MSR, NW); Department of Medicine, University of Florida Health, Gainesville, FL (CJA); NRG Oncology and the University of Pittsburgh Graduate School of Public Health, Department of Biostatistics, Pittsburgh, PA (GY); Glendale Memorial Hospital, Glendale, CA (RWB); CCOP Christiana Care Health Systems, Newark, DE (TFW); Mayo Clinic, Rochester, MN and the ALLIANCE, Boston, MA (HCP); Wayne State University, Karmanos Cancer Institute, Detroit, MI and SWOG, San Antonio, TX (AFS); Emory University, Department of Radiation Oncology, Atlanta, GA and ECOG/ACRIN, Rochester, MN (JCL); Massachusetts General Hospital Cancer Center and the ALLIANCE, Boston, MA (DPR); Kaiser Permanente, Fremont, CA (AA); Novant Health Forsyth Medical Center, Winston-Salem, NC (LSE); University of Pittsburgh, Pittsburgh, PA (NB); Missouri Valley Cancer Consortium CCOP, Omaha, NE (GS); Florida Cancer Specialists, Fort Myers, FL (JFE); Beaumont Hospital System, Royal Oak, MI (JMR); Cancer Center of Kansas, Wichita, KS (DFMJr); Stroger Hospital Chicago MU-NCORP, Chicago, IL (MRM); Montana Cancer Consortium, Billings, MT (BTM); Oncology and Hematology Care, Cincinnati, OH (PJW); UF Health Cancer Center, Orlando FL (MSR); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (NW)
| | - Jerome C Landry
- NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA (CJA, GY, MJO, RWB, TFW, HCP, AFS, JCL, DPR, AA, LSE, NB, GS, JFE, JMR, DFMJr, MRM, BTM, PJW, SS, MSR, NW); Department of Medicine, University of Florida Health, Gainesville, FL (CJA); NRG Oncology and the University of Pittsburgh Graduate School of Public Health, Department of Biostatistics, Pittsburgh, PA (GY); Glendale Memorial Hospital, Glendale, CA (RWB); CCOP Christiana Care Health Systems, Newark, DE (TFW); Mayo Clinic, Rochester, MN and the ALLIANCE, Boston, MA (HCP); Wayne State University, Karmanos Cancer Institute, Detroit, MI and SWOG, San Antonio, TX (AFS); Emory University, Department of Radiation Oncology, Atlanta, GA and ECOG/ACRIN, Rochester, MN (JCL); Massachusetts General Hospital Cancer Center and the ALLIANCE, Boston, MA (DPR); Kaiser Permanente, Fremont, CA (AA); Novant Health Forsyth Medical Center, Winston-Salem, NC (LSE); University of Pittsburgh, Pittsburgh, PA (NB); Missouri Valley Cancer Consortium CCOP, Omaha, NE (GS); Florida Cancer Specialists, Fort Myers, FL (JFE); Beaumont Hospital System, Royal Oak, MI (JMR); Cancer Center of Kansas, Wichita, KS (DFMJr); Stroger Hospital Chicago MU-NCORP, Chicago, IL (MRM); Montana Cancer Consortium, Billings, MT (BTM); Oncology and Hematology Care, Cincinnati, OH (PJW); UF Health Cancer Center, Orlando FL (MSR); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (NW)
| | - David P Ryan
- NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA (CJA, GY, MJO, RWB, TFW, HCP, AFS, JCL, DPR, AA, LSE, NB, GS, JFE, JMR, DFMJr, MRM, BTM, PJW, SS, MSR, NW); Department of Medicine, University of Florida Health, Gainesville, FL (CJA); NRG Oncology and the University of Pittsburgh Graduate School of Public Health, Department of Biostatistics, Pittsburgh, PA (GY); Glendale Memorial Hospital, Glendale, CA (RWB); CCOP Christiana Care Health Systems, Newark, DE (TFW); Mayo Clinic, Rochester, MN and the ALLIANCE, Boston, MA (HCP); Wayne State University, Karmanos Cancer Institute, Detroit, MI and SWOG, San Antonio, TX (AFS); Emory University, Department of Radiation Oncology, Atlanta, GA and ECOG/ACRIN, Rochester, MN (JCL); Massachusetts General Hospital Cancer Center and the ALLIANCE, Boston, MA (DPR); Kaiser Permanente, Fremont, CA (AA); Novant Health Forsyth Medical Center, Winston-Salem, NC (LSE); University of Pittsburgh, Pittsburgh, PA (NB); Missouri Valley Cancer Consortium CCOP, Omaha, NE (GS); Florida Cancer Specialists, Fort Myers, FL (JFE); Beaumont Hospital System, Royal Oak, MI (JMR); Cancer Center of Kansas, Wichita, KS (DFMJr); Stroger Hospital Chicago MU-NCORP, Chicago, IL (MRM); Montana Cancer Consortium, Billings, MT (BTM); Oncology and Hematology Care, Cincinnati, OH (PJW); UF Health Cancer Center, Orlando FL (MSR); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (NW)
| | - Amit Arora
- NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA (CJA, GY, MJO, RWB, TFW, HCP, AFS, JCL, DPR, AA, LSE, NB, GS, JFE, JMR, DFMJr, MRM, BTM, PJW, SS, MSR, NW); Department of Medicine, University of Florida Health, Gainesville, FL (CJA); NRG Oncology and the University of Pittsburgh Graduate School of Public Health, Department of Biostatistics, Pittsburgh, PA (GY); Glendale Memorial Hospital, Glendale, CA (RWB); CCOP Christiana Care Health Systems, Newark, DE (TFW); Mayo Clinic, Rochester, MN and the ALLIANCE, Boston, MA (HCP); Wayne State University, Karmanos Cancer Institute, Detroit, MI and SWOG, San Antonio, TX (AFS); Emory University, Department of Radiation Oncology, Atlanta, GA and ECOG/ACRIN, Rochester, MN (JCL); Massachusetts General Hospital Cancer Center and the ALLIANCE, Boston, MA (DPR); Kaiser Permanente, Fremont, CA (AA); Novant Health Forsyth Medical Center, Winston-Salem, NC (LSE); University of Pittsburgh, Pittsburgh, PA (NB); Missouri Valley Cancer Consortium CCOP, Omaha, NE (GS); Florida Cancer Specialists, Fort Myers, FL (JFE); Beaumont Hospital System, Royal Oak, MI (JMR); Cancer Center of Kansas, Wichita, KS (DFMJr); Stroger Hospital Chicago MU-NCORP, Chicago, IL (MRM); Montana Cancer Consortium, Billings, MT (BTM); Oncology and Hematology Care, Cincinnati, OH (PJW); UF Health Cancer Center, Orlando FL (MSR); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (NW)
| | - Lisa S Evans
- NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA (CJA, GY, MJO, RWB, TFW, HCP, AFS, JCL, DPR, AA, LSE, NB, GS, JFE, JMR, DFMJr, MRM, BTM, PJW, SS, MSR, NW); Department of Medicine, University of Florida Health, Gainesville, FL (CJA); NRG Oncology and the University of Pittsburgh Graduate School of Public Health, Department of Biostatistics, Pittsburgh, PA (GY); Glendale Memorial Hospital, Glendale, CA (RWB); CCOP Christiana Care Health Systems, Newark, DE (TFW); Mayo Clinic, Rochester, MN and the ALLIANCE, Boston, MA (HCP); Wayne State University, Karmanos Cancer Institute, Detroit, MI and SWOG, San Antonio, TX (AFS); Emory University, Department of Radiation Oncology, Atlanta, GA and ECOG/ACRIN, Rochester, MN (JCL); Massachusetts General Hospital Cancer Center and the ALLIANCE, Boston, MA (DPR); Kaiser Permanente, Fremont, CA (AA); Novant Health Forsyth Medical Center, Winston-Salem, NC (LSE); University of Pittsburgh, Pittsburgh, PA (NB); Missouri Valley Cancer Consortium CCOP, Omaha, NE (GS); Florida Cancer Specialists, Fort Myers, FL (JFE); Beaumont Hospital System, Royal Oak, MI (JMR); Cancer Center of Kansas, Wichita, KS (DFMJr); Stroger Hospital Chicago MU-NCORP, Chicago, IL (MRM); Montana Cancer Consortium, Billings, MT (BTM); Oncology and Hematology Care, Cincinnati, OH (PJW); UF Health Cancer Center, Orlando FL (MSR); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (NW)
| | - Nathan Bahary
- NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA (CJA, GY, MJO, RWB, TFW, HCP, AFS, JCL, DPR, AA, LSE, NB, GS, JFE, JMR, DFMJr, MRM, BTM, PJW, SS, MSR, NW); Department of Medicine, University of Florida Health, Gainesville, FL (CJA); NRG Oncology and the University of Pittsburgh Graduate School of Public Health, Department of Biostatistics, Pittsburgh, PA (GY); Glendale Memorial Hospital, Glendale, CA (RWB); CCOP Christiana Care Health Systems, Newark, DE (TFW); Mayo Clinic, Rochester, MN and the ALLIANCE, Boston, MA (HCP); Wayne State University, Karmanos Cancer Institute, Detroit, MI and SWOG, San Antonio, TX (AFS); Emory University, Department of Radiation Oncology, Atlanta, GA and ECOG/ACRIN, Rochester, MN (JCL); Massachusetts General Hospital Cancer Center and the ALLIANCE, Boston, MA (DPR); Kaiser Permanente, Fremont, CA (AA); Novant Health Forsyth Medical Center, Winston-Salem, NC (LSE); University of Pittsburgh, Pittsburgh, PA (NB); Missouri Valley Cancer Consortium CCOP, Omaha, NE (GS); Florida Cancer Specialists, Fort Myers, FL (JFE); Beaumont Hospital System, Royal Oak, MI (JMR); Cancer Center of Kansas, Wichita, KS (DFMJr); Stroger Hospital Chicago MU-NCORP, Chicago, IL (MRM); Montana Cancer Consortium, Billings, MT (BTM); Oncology and Hematology Care, Cincinnati, OH (PJW); UF Health Cancer Center, Orlando FL (MSR); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (NW)
| | - Gamini Soori
- NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA (CJA, GY, MJO, RWB, TFW, HCP, AFS, JCL, DPR, AA, LSE, NB, GS, JFE, JMR, DFMJr, MRM, BTM, PJW, SS, MSR, NW); Department of Medicine, University of Florida Health, Gainesville, FL (CJA); NRG Oncology and the University of Pittsburgh Graduate School of Public Health, Department of Biostatistics, Pittsburgh, PA (GY); Glendale Memorial Hospital, Glendale, CA (RWB); CCOP Christiana Care Health Systems, Newark, DE (TFW); Mayo Clinic, Rochester, MN and the ALLIANCE, Boston, MA (HCP); Wayne State University, Karmanos Cancer Institute, Detroit, MI and SWOG, San Antonio, TX (AFS); Emory University, Department of Radiation Oncology, Atlanta, GA and ECOG/ACRIN, Rochester, MN (JCL); Massachusetts General Hospital Cancer Center and the ALLIANCE, Boston, MA (DPR); Kaiser Permanente, Fremont, CA (AA); Novant Health Forsyth Medical Center, Winston-Salem, NC (LSE); University of Pittsburgh, Pittsburgh, PA (NB); Missouri Valley Cancer Consortium CCOP, Omaha, NE (GS); Florida Cancer Specialists, Fort Myers, FL (JFE); Beaumont Hospital System, Royal Oak, MI (JMR); Cancer Center of Kansas, Wichita, KS (DFMJr); Stroger Hospital Chicago MU-NCORP, Chicago, IL (MRM); Montana Cancer Consortium, Billings, MT (BTM); Oncology and Hematology Care, Cincinnati, OH (PJW); UF Health Cancer Center, Orlando FL (MSR); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (NW)
| | - Janice F Eakle
- NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA (CJA, GY, MJO, RWB, TFW, HCP, AFS, JCL, DPR, AA, LSE, NB, GS, JFE, JMR, DFMJr, MRM, BTM, PJW, SS, MSR, NW); Department of Medicine, University of Florida Health, Gainesville, FL (CJA); NRG Oncology and the University of Pittsburgh Graduate School of Public Health, Department of Biostatistics, Pittsburgh, PA (GY); Glendale Memorial Hospital, Glendale, CA (RWB); CCOP Christiana Care Health Systems, Newark, DE (TFW); Mayo Clinic, Rochester, MN and the ALLIANCE, Boston, MA (HCP); Wayne State University, Karmanos Cancer Institute, Detroit, MI and SWOG, San Antonio, TX (AFS); Emory University, Department of Radiation Oncology, Atlanta, GA and ECOG/ACRIN, Rochester, MN (JCL); Massachusetts General Hospital Cancer Center and the ALLIANCE, Boston, MA (DPR); Kaiser Permanente, Fremont, CA (AA); Novant Health Forsyth Medical Center, Winston-Salem, NC (LSE); University of Pittsburgh, Pittsburgh, PA (NB); Missouri Valley Cancer Consortium CCOP, Omaha, NE (GS); Florida Cancer Specialists, Fort Myers, FL (JFE); Beaumont Hospital System, Royal Oak, MI (JMR); Cancer Center of Kansas, Wichita, KS (DFMJr); Stroger Hospital Chicago MU-NCORP, Chicago, IL (MRM); Montana Cancer Consortium, Billings, MT (BTM); Oncology and Hematology Care, Cincinnati, OH (PJW); UF Health Cancer Center, Orlando FL (MSR); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (NW)
| | - John M Robertson
- NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA (CJA, GY, MJO, RWB, TFW, HCP, AFS, JCL, DPR, AA, LSE, NB, GS, JFE, JMR, DFMJr, MRM, BTM, PJW, SS, MSR, NW); Department of Medicine, University of Florida Health, Gainesville, FL (CJA); NRG Oncology and the University of Pittsburgh Graduate School of Public Health, Department of Biostatistics, Pittsburgh, PA (GY); Glendale Memorial Hospital, Glendale, CA (RWB); CCOP Christiana Care Health Systems, Newark, DE (TFW); Mayo Clinic, Rochester, MN and the ALLIANCE, Boston, MA (HCP); Wayne State University, Karmanos Cancer Institute, Detroit, MI and SWOG, San Antonio, TX (AFS); Emory University, Department of Radiation Oncology, Atlanta, GA and ECOG/ACRIN, Rochester, MN (JCL); Massachusetts General Hospital Cancer Center and the ALLIANCE, Boston, MA (DPR); Kaiser Permanente, Fremont, CA (AA); Novant Health Forsyth Medical Center, Winston-Salem, NC (LSE); University of Pittsburgh, Pittsburgh, PA (NB); Missouri Valley Cancer Consortium CCOP, Omaha, NE (GS); Florida Cancer Specialists, Fort Myers, FL (JFE); Beaumont Hospital System, Royal Oak, MI (JMR); Cancer Center of Kansas, Wichita, KS (DFMJr); Stroger Hospital Chicago MU-NCORP, Chicago, IL (MRM); Montana Cancer Consortium, Billings, MT (BTM); Oncology and Hematology Care, Cincinnati, OH (PJW); UF Health Cancer Center, Orlando FL (MSR); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (NW)
| | - Dennis F Moore
- NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA (CJA, GY, MJO, RWB, TFW, HCP, AFS, JCL, DPR, AA, LSE, NB, GS, JFE, JMR, DFMJr, MRM, BTM, PJW, SS, MSR, NW); Department of Medicine, University of Florida Health, Gainesville, FL (CJA); NRG Oncology and the University of Pittsburgh Graduate School of Public Health, Department of Biostatistics, Pittsburgh, PA (GY); Glendale Memorial Hospital, Glendale, CA (RWB); CCOP Christiana Care Health Systems, Newark, DE (TFW); Mayo Clinic, Rochester, MN and the ALLIANCE, Boston, MA (HCP); Wayne State University, Karmanos Cancer Institute, Detroit, MI and SWOG, San Antonio, TX (AFS); Emory University, Department of Radiation Oncology, Atlanta, GA and ECOG/ACRIN, Rochester, MN (JCL); Massachusetts General Hospital Cancer Center and the ALLIANCE, Boston, MA (DPR); Kaiser Permanente, Fremont, CA (AA); Novant Health Forsyth Medical Center, Winston-Salem, NC (LSE); University of Pittsburgh, Pittsburgh, PA (NB); Missouri Valley Cancer Consortium CCOP, Omaha, NE (GS); Florida Cancer Specialists, Fort Myers, FL (JFE); Beaumont Hospital System, Royal Oak, MI (JMR); Cancer Center of Kansas, Wichita, KS (DFMJr); Stroger Hospital Chicago MU-NCORP, Chicago, IL (MRM); Montana Cancer Consortium, Billings, MT (BTM); Oncology and Hematology Care, Cincinnati, OH (PJW); UF Health Cancer Center, Orlando FL (MSR); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (NW)
| | - Michael R Mullane
- NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA (CJA, GY, MJO, RWB, TFW, HCP, AFS, JCL, DPR, AA, LSE, NB, GS, JFE, JMR, DFMJr, MRM, BTM, PJW, SS, MSR, NW); Department of Medicine, University of Florida Health, Gainesville, FL (CJA); NRG Oncology and the University of Pittsburgh Graduate School of Public Health, Department of Biostatistics, Pittsburgh, PA (GY); Glendale Memorial Hospital, Glendale, CA (RWB); CCOP Christiana Care Health Systems, Newark, DE (TFW); Mayo Clinic, Rochester, MN and the ALLIANCE, Boston, MA (HCP); Wayne State University, Karmanos Cancer Institute, Detroit, MI and SWOG, San Antonio, TX (AFS); Emory University, Department of Radiation Oncology, Atlanta, GA and ECOG/ACRIN, Rochester, MN (JCL); Massachusetts General Hospital Cancer Center and the ALLIANCE, Boston, MA (DPR); Kaiser Permanente, Fremont, CA (AA); Novant Health Forsyth Medical Center, Winston-Salem, NC (LSE); University of Pittsburgh, Pittsburgh, PA (NB); Missouri Valley Cancer Consortium CCOP, Omaha, NE (GS); Florida Cancer Specialists, Fort Myers, FL (JFE); Beaumont Hospital System, Royal Oak, MI (JMR); Cancer Center of Kansas, Wichita, KS (DFMJr); Stroger Hospital Chicago MU-NCORP, Chicago, IL (MRM); Montana Cancer Consortium, Billings, MT (BTM); Oncology and Hematology Care, Cincinnati, OH (PJW); UF Health Cancer Center, Orlando FL (MSR); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (NW)
| | - Benjamin T Marchello
- NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA (CJA, GY, MJO, RWB, TFW, HCP, AFS, JCL, DPR, AA, LSE, NB, GS, JFE, JMR, DFMJr, MRM, BTM, PJW, SS, MSR, NW); Department of Medicine, University of Florida Health, Gainesville, FL (CJA); NRG Oncology and the University of Pittsburgh Graduate School of Public Health, Department of Biostatistics, Pittsburgh, PA (GY); Glendale Memorial Hospital, Glendale, CA (RWB); CCOP Christiana Care Health Systems, Newark, DE (TFW); Mayo Clinic, Rochester, MN and the ALLIANCE, Boston, MA (HCP); Wayne State University, Karmanos Cancer Institute, Detroit, MI and SWOG, San Antonio, TX (AFS); Emory University, Department of Radiation Oncology, Atlanta, GA and ECOG/ACRIN, Rochester, MN (JCL); Massachusetts General Hospital Cancer Center and the ALLIANCE, Boston, MA (DPR); Kaiser Permanente, Fremont, CA (AA); Novant Health Forsyth Medical Center, Winston-Salem, NC (LSE); University of Pittsburgh, Pittsburgh, PA (NB); Missouri Valley Cancer Consortium CCOP, Omaha, NE (GS); Florida Cancer Specialists, Fort Myers, FL (JFE); Beaumont Hospital System, Royal Oak, MI (JMR); Cancer Center of Kansas, Wichita, KS (DFMJr); Stroger Hospital Chicago MU-NCORP, Chicago, IL (MRM); Montana Cancer Consortium, Billings, MT (BTM); Oncology and Hematology Care, Cincinnati, OH (PJW); UF Health Cancer Center, Orlando FL (MSR); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (NW)
| | - Patrick J Ward
- NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA (CJA, GY, MJO, RWB, TFW, HCP, AFS, JCL, DPR, AA, LSE, NB, GS, JFE, JMR, DFMJr, MRM, BTM, PJW, SS, MSR, NW); Department of Medicine, University of Florida Health, Gainesville, FL (CJA); NRG Oncology and the University of Pittsburgh Graduate School of Public Health, Department of Biostatistics, Pittsburgh, PA (GY); Glendale Memorial Hospital, Glendale, CA (RWB); CCOP Christiana Care Health Systems, Newark, DE (TFW); Mayo Clinic, Rochester, MN and the ALLIANCE, Boston, MA (HCP); Wayne State University, Karmanos Cancer Institute, Detroit, MI and SWOG, San Antonio, TX (AFS); Emory University, Department of Radiation Oncology, Atlanta, GA and ECOG/ACRIN, Rochester, MN (JCL); Massachusetts General Hospital Cancer Center and the ALLIANCE, Boston, MA (DPR); Kaiser Permanente, Fremont, CA (AA); Novant Health Forsyth Medical Center, Winston-Salem, NC (LSE); University of Pittsburgh, Pittsburgh, PA (NB); Missouri Valley Cancer Consortium CCOP, Omaha, NE (GS); Florida Cancer Specialists, Fort Myers, FL (JFE); Beaumont Hospital System, Royal Oak, MI (JMR); Cancer Center of Kansas, Wichita, KS (DFMJr); Stroger Hospital Chicago MU-NCORP, Chicago, IL (MRM); Montana Cancer Consortium, Billings, MT (BTM); Oncology and Hematology Care, Cincinnati, OH (PJW); UF Health Cancer Center, Orlando FL (MSR); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (NW)
| | - Saima Sharif
- NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA (CJA, GY, MJO, RWB, TFW, HCP, AFS, JCL, DPR, AA, LSE, NB, GS, JFE, JMR, DFMJr, MRM, BTM, PJW, SS, MSR, NW); Department of Medicine, University of Florida Health, Gainesville, FL (CJA); NRG Oncology and the University of Pittsburgh Graduate School of Public Health, Department of Biostatistics, Pittsburgh, PA (GY); Glendale Memorial Hospital, Glendale, CA (RWB); CCOP Christiana Care Health Systems, Newark, DE (TFW); Mayo Clinic, Rochester, MN and the ALLIANCE, Boston, MA (HCP); Wayne State University, Karmanos Cancer Institute, Detroit, MI and SWOG, San Antonio, TX (AFS); Emory University, Department of Radiation Oncology, Atlanta, GA and ECOG/ACRIN, Rochester, MN (JCL); Massachusetts General Hospital Cancer Center and the ALLIANCE, Boston, MA (DPR); Kaiser Permanente, Fremont, CA (AA); Novant Health Forsyth Medical Center, Winston-Salem, NC (LSE); University of Pittsburgh, Pittsburgh, PA (NB); Missouri Valley Cancer Consortium CCOP, Omaha, NE (GS); Florida Cancer Specialists, Fort Myers, FL (JFE); Beaumont Hospital System, Royal Oak, MI (JMR); Cancer Center of Kansas, Wichita, KS (DFMJr); Stroger Hospital Chicago MU-NCORP, Chicago, IL (MRM); Montana Cancer Consortium, Billings, MT (BTM); Oncology and Hematology Care, Cincinnati, OH (PJW); UF Health Cancer Center, Orlando FL (MSR); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (NW)
| | - Mark S Roh
- NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA (CJA, GY, MJO, RWB, TFW, HCP, AFS, JCL, DPR, AA, LSE, NB, GS, JFE, JMR, DFMJr, MRM, BTM, PJW, SS, MSR, NW); Department of Medicine, University of Florida Health, Gainesville, FL (CJA); NRG Oncology and the University of Pittsburgh Graduate School of Public Health, Department of Biostatistics, Pittsburgh, PA (GY); Glendale Memorial Hospital, Glendale, CA (RWB); CCOP Christiana Care Health Systems, Newark, DE (TFW); Mayo Clinic, Rochester, MN and the ALLIANCE, Boston, MA (HCP); Wayne State University, Karmanos Cancer Institute, Detroit, MI and SWOG, San Antonio, TX (AFS); Emory University, Department of Radiation Oncology, Atlanta, GA and ECOG/ACRIN, Rochester, MN (JCL); Massachusetts General Hospital Cancer Center and the ALLIANCE, Boston, MA (DPR); Kaiser Permanente, Fremont, CA (AA); Novant Health Forsyth Medical Center, Winston-Salem, NC (LSE); University of Pittsburgh, Pittsburgh, PA (NB); Missouri Valley Cancer Consortium CCOP, Omaha, NE (GS); Florida Cancer Specialists, Fort Myers, FL (JFE); Beaumont Hospital System, Royal Oak, MI (JMR); Cancer Center of Kansas, Wichita, KS (DFMJr); Stroger Hospital Chicago MU-NCORP, Chicago, IL (MRM); Montana Cancer Consortium, Billings, MT (BTM); Oncology and Hematology Care, Cincinnati, OH (PJW); UF Health Cancer Center, Orlando FL (MSR); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (NW)
| | - Norman Wolmark
- NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA (CJA, GY, MJO, RWB, TFW, HCP, AFS, JCL, DPR, AA, LSE, NB, GS, JFE, JMR, DFMJr, MRM, BTM, PJW, SS, MSR, NW); Department of Medicine, University of Florida Health, Gainesville, FL (CJA); NRG Oncology and the University of Pittsburgh Graduate School of Public Health, Department of Biostatistics, Pittsburgh, PA (GY); Glendale Memorial Hospital, Glendale, CA (RWB); CCOP Christiana Care Health Systems, Newark, DE (TFW); Mayo Clinic, Rochester, MN and the ALLIANCE, Boston, MA (HCP); Wayne State University, Karmanos Cancer Institute, Detroit, MI and SWOG, San Antonio, TX (AFS); Emory University, Department of Radiation Oncology, Atlanta, GA and ECOG/ACRIN, Rochester, MN (JCL); Massachusetts General Hospital Cancer Center and the ALLIANCE, Boston, MA (DPR); Kaiser Permanente, Fremont, CA (AA); Novant Health Forsyth Medical Center, Winston-Salem, NC (LSE); University of Pittsburgh, Pittsburgh, PA (NB); Missouri Valley Cancer Consortium CCOP, Omaha, NE (GS); Florida Cancer Specialists, Fort Myers, FL (JFE); Beaumont Hospital System, Royal Oak, MI (JMR); Cancer Center of Kansas, Wichita, KS (DFMJr); Stroger Hospital Chicago MU-NCORP, Chicago, IL (MRM); Montana Cancer Consortium, Billings, MT (BTM); Oncology and Hematology Care, Cincinnati, OH (PJW); UF Health Cancer Center, Orlando FL (MSR); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (NW)
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Postoperative Capecitabine with Concurrent Intensity-Modulated Radiotherapy or Three-Dimensional Conformal Radiotherapy for Patients with Stage II and III Rectal Cancer. PLoS One 2015; 10:e0124601. [PMID: 25915948 PMCID: PMC4411062 DOI: 10.1371/journal.pone.0124601] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2014] [Accepted: 03/04/2015] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND The aim of this study was to evaluate the survival outcomes and toxicity of postoperative chemoradiotherapy with capecitabine and concurrent intensity-modulated radiotherapy (IMRT) or three-dimensional conformal radiotherapy (3D-CRT) in patients with stage II and III rectal cancer. PATIENTS We recruited 184 patients with pathologically proven, stage II or III rectal cancer. Following total mesorectal excision (TME), the patients were treated with capecitabine and concurrent IMRT/3D-CRT. The treatment regimen consisted of two cycles of oral capecitabine (1600 mg/m2/day), administered twice daily from day 1-14 of radiotherapy, followed by a 7-day rest. The median pelvic dose was 50 Gy in 25 fractions. Oxaliplatin-based adjuvant chemotherapy was administered after the chemoradiotherapy. RESULTS The 5-year overall survival, disease-free survival and locoregional control (LRC) rates were 85.1%, 80% and 95.4%, respectively. Grade 3 and 4 toxicities were observed in 28.3% of patients during treatment. Grade 3 or 4 late toxicity, including neurotoxicity or gastrointestinal toxicity, was only observed in nine patients (4.9%). CONCLUSIONS This study demonstrated that capecitabine chemotherapy with concurrent IMRT/3D-CRT following TME is safe, is well tolerated and achieves superior LRC and favorable survival rates, with acceptable toxicity.
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Jin T, Zhu Y, Luo JL, Zhou N, Li DC, Ju HX, Fan YT, Liu Y, Zhu YP, Feng HY, Liu LY. Prospective phase II trial of nimotuzumab in combination with radiotherapy and concurrent capecitabine in locally advanced rectal cancer. Int J Colorectal Dis 2015; 30:337-45. [PMID: 25564344 DOI: 10.1007/s00384-014-2097-2] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/11/2014] [Indexed: 02/04/2023]
Abstract
PURPOSE The aim of the study was to evaluate the safety and efficacy of adding concurrent nimotuzumab to preoperative radiotherapy with concurrent capecitabine in locally advanced rectal cancer. METHODS AND MATERIALS Patients with rectal cancer (clinical stage T3/4 or N+) were scheduled to receive weekly nimotuzumab (400 mg; days -6, 1, 8, 15, 22, and 29). Capecitabine (825 mg/m(2)) was delivered orally twice daily for the duration of radiotherapy. Radiotherapy was administered at 50.4 Gy (45 + 5.4 Gy). The main endpoint was the pathologic complete response (pCR) rate. RESULTS Twenty-one patients with T3 or T4 disease were enrolled; 66.7 % were nodal-positive; the median distance from the anal verge was 5.5 cm. A pCR was achieved in four patients (19.0 %); 71.4 % patients obtained moderate or good tumor regression (Grade 2 and 3). Downstaging occurred in 15/21 (71.4 %) patients by T stage and 11/14 (78.6 %) by N stage. The actual dose intensities (median/mean, %) were nimotuzumab (100, 100) and capecitabine (100, 99.5). The most frequent Grade 1/2 toxicities were radiation dermatitis (57.1 %), nausea/vomiting (52.4 %), leukocytopenia (47.6 %), diarrhea (47.6 %), and proctitis (38.1 %). Grade 3 diarrhea was observed in 9.5 % of patients and Grade 3 leukocytopenia in 4.8 %. CONCLUSION These preliminary results indicate that nimotuzumab can be safely combined with radiotherapy plus concurrent capecitabine. The efficacy of this regimen (pCR = 19.0 %) was significantly higher than that observed in previous phase II trials of preoperative radiotherapy with concurrent capecitabine and cetuximab in rectal cancer. Further investigation of concurrent nimotuzumab with radiotherapy plus capecitabine is warranted.
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Affiliation(s)
- Ting Jin
- Department of Radiation Oncology, Zhejiang Cancer Hospital, 38 Guang Ji Road, Hangzhou, 310022, Zhejiang, People's Republic of China
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15
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Miki Y, Maeda K, Hosono M, Nagahara H, Hirakawa K, Shimatani Y, Tsutsumi S, Miki Y. Neoadjuvant capecitabine, bevacizumab and radiotherapy for locally advanced rectal cancer: results of a single-institute Phase I study. JOURNAL OF RADIATION RESEARCH 2014; 55:1171-1177. [PMID: 25129557 PMCID: PMC4229928 DOI: 10.1093/jrr/rru063] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/08/2013] [Revised: 06/11/2014] [Accepted: 06/17/2014] [Indexed: 06/03/2023]
Abstract
The aim of this Phase I clinical trial was to assess the feasibility and safety of capecitabine-based preoperative chemoradiotherapy (CRT) combined with bevacizumab and to determine the optimal capecitabine dose for Japanese patients with locally advanced rectal cancer. Patients with cT3/T4 rectal cancer were eligible. Bevacizumab was administered at 5 mg/kg intravenously on Days 1, 15 and 29. Capecitabine was administered on weekdays concurrently with pelvic radiotherapy at a daily dose of 1.8 Gy, totally to 50.4 Gy. Capecitabine was initiated at 825 mg/m(2) twice daily at Dose Level 1, with a planned escalation to 900 mg/m(2) twice daily at Dose Level 2. Within 6.1-10.3 (median, 9.4) weeks after the completion of the CRT, surgery was performed. Three patients were enrolled at each dose level. Regarding the CRT-related acute toxicities, all of the adverse events were limited to Grade 1. There was no Grade 2 or greater toxicity. No patient needed attenuation or interruption of bevacizumab, capecitabine or radiation. All of the patients received the scheduled dose of CRT. All of the patients underwent R0 resection. Two (33.3%) of the six patients had a pathological complete response, and five (83.3%) patients experienced downstaging. In total, three patients (50%) developed postoperative complications. One patient developed an intrapelvic abscess and healed with incisional drainage. The other two patients healed following conservative treatment. This regimen was safely performed as preoperative CRT for Japanese patients with locally advanced rectal cancer. The recommended capecitabine dose is 900 mg/m(2) twice daily.
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Affiliation(s)
- Yoshitaka Miki
- Department of Radiology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan
| | - Kiyoshi Maeda
- Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
| | - Masako Hosono
- Department of Radiology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan
| | - Hisashi Nagahara
- Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
| | - Kosei Hirakawa
- Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
| | - Yasuhiko Shimatani
- Department of Radiology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan
| | - Shinichi Tsutsumi
- Department of Radiology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan
| | - Yukio Miki
- Department of Radiology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan
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16
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Burbach JPM, den Harder AM, Intven M, van Vulpen M, Verkooijen HM, Reerink O. Impact of radiotherapy boost on pathological complete response in patients with locally advanced rectal cancer: a systematic review and meta-analysis. Radiother Oncol 2014; 113:1-9. [PMID: 25281582 DOI: 10.1016/j.radonc.2014.08.035] [Citation(s) in RCA: 115] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2014] [Revised: 08/25/2014] [Accepted: 08/31/2014] [Indexed: 02/07/2023]
Abstract
PURPOSE We conducted a systematic review and meta-analysis to quantify the pathological complete response (pCR) rate after preoperative (chemo)radiation with doses of ⩾60Gy in patients with locally advanced rectal cancer. Complete response is relevant since this could select a proportion of patients for which organ-preserving strategies might be possible. Furthermore, we investigated correlations between EQD2 dose and pCR-rate, toxicity or resectability, and additionally between pCR-rate and chemotherapy, boost-approach or surgical-interval. METHODS AND MATERIALS PubMed, EMBASE and Cochrane libraries were searched with the terms 'radiotherapy', 'boost' and 'rectal cancer' and synonym terms. Studies delivering a preoperative dose of ⩾60 Gy were eligible for inclusion. Original English full texts that allowed intention-to-treat pCR-rate calculation were included. Study variables, including pCR, acute grade ⩾3 toxicity and resectability-rate, were extracted by two authors independently. Eligibility for meta-analysis was assessed by critical appraisal. Heterogeneity and pooled estimates were calculated for all three outcomes. Pearson correlation coefficients were calculated between the variables mentioned earlier. RESULTS The search identified 3377 original articles, of which 18 met our inclusion criteria (1106 patients). Fourteen studies were included for meta-analysis (487 patients treated with ⩾60 Gy). pCR-rate ranged between 0.0% and 44.4%. Toxicity ranged between 1.3% and 43.8% and resectability-rate between 34.0% and 100%. Pooled pCR-rate was 20.4% (95% CI 16.8-24.5%), with low heterogeneity (I2 0.0%, 95% CI 0.00-84.0%). Pooled acute grade ⩾3 toxicity was 10.3% (95% CI 5.4-18.6%) and pooled resectability-rate was 89.5% (95% CI 78.2-95.3%). CONCLUSION Dose escalation above 60 Gy for locally advanced rectal cancer results in high pCR-rates and acceptable early toxicity. This observation needs to be further investigated within larger randomized controlled phase 3 trials in the future.
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Affiliation(s)
| | | | - Martijn Intven
- Department of Radiation Oncology, University Medical Center, Utrecht, The Netherlands
| | - Marco van Vulpen
- Department of Radiation Oncology, University Medical Center, Utrecht, The Netherlands
| | | | - Onne Reerink
- Department of Radiation Oncology, University Medical Center, Utrecht, The Netherlands
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Sadahiro S, Suzuki T, Tanaka A, Okada K, Saito G, Kamijo A, Akiba T, Kawada S. Phase II study of preoperative concurrent chemoradiotherapy with S-1 plus bevacizumab for locally advanced resectable rectal adenocarcinoma. Oncology 2014; 88:49-56. [PMID: 25277532 DOI: 10.1159/000367972] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2014] [Accepted: 08/27/2014] [Indexed: 11/19/2022]
Abstract
OBJECTIVE A single-arm phase II clinical trial was conducted to evaluate the safety and efficacy of preoperative chemoradiotherapy (CRT) with concurrent S-1, bevacizumab, and radiation in patients with locally advanced rectal cancer (LARC). METHODS Fifty-two patients with LARC were enrolled. A total dose of 45 Gy was delivered in 25 fractions over 5 weeks, S-1 was administered orally twice a day on days 1-14 and 22-35, and bevacizumab was administered on days 1, 15, and 29. Surgical resection was scheduled 8 weeks (6-10 weeks) after completing the CRT. RESULTS All 52 patients underwent R0 radical surgery. Sphincter preservation was possible in 38 (73.1%) patients. A pathologic complete response was obtained in 10 (19.2%) patients, a pathologic downstaging was achieved in 37 (71.2%) patients, and the tumor shrinkage rate was 77.1%. The only grade 3 adverse events were leukopenia and rash in 1 (1.9%) patient. The rate of postoperative complications was 28.8%. Anastomotic leakage occurred in 9 (23.7%) of the 38 patients who underwent sphincter-preserving surgery. Perineal wound dehiscence developed in 2 (14.3%) of the 14 patients who received an abdominoperineal resection. CONCLUSIONS Adding bevacizumab to S-1 clearly increased the incidence of wound-related complications, with no distinct enhancement of tumor response.
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Nakamura T, Yamashita K, Sato T, Ema A, Naito M, Watanabe M. Neoadjuvant chemoradiation therapy using concurrent S-1 and irinotecan in rectal cancer: impact on long-term clinical outcomes and prognostic factors. Int J Radiat Oncol Biol Phys 2014; 89:547-55. [PMID: 24929164 DOI: 10.1016/j.ijrobp.2014.03.007] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2013] [Revised: 02/27/2014] [Accepted: 03/06/2014] [Indexed: 01/08/2023]
Abstract
PURPOSE To assess the long-term outcomes of patients with rectal cancer who received neoadjuvant chemoradiation therapy (NCRT) with concurrent S-1 and irinotecan (S-1/irinotecan) therapy. METHODS AND MATERIALS The study group consisted of 115 patients with clinical stage T3 or T4 rectal cancer. Patients received pelvic radiation therapy (45 Gy) plus concurrent oral S-1/irinotecan. The median follow-up was 60 months. RESULTS Grade 3 adverse effects occurred in 7 patients (6%), and the completion rate of NCRT was 87%. All 115 patients (100%) were able to undergo R0 surgical resection. Twenty-eight patients (24%) had a pathological complete response (ypCR). At 60 months, the local recurrence-free survival was 93%, disease-free survival (DFS) was 79%, and overall survival (OS) was 80%. On multivariate analysis with a proportional hazards model, ypN2 was the only independent prognostic factor for DFS (P=.0019) and OS (P=.0064) in the study group as a whole. Multivariate analysis was additionally performed for the subgroup of 106 patients with ypN0/1 disease, who had a DFS rate of 85.3%. Both ypT (P=.0065) and tumor location (P=.003) were independent predictors of DFS. A combination of these factors was very strongly related to high risk of recurrence (P<.0001), which occurred most commonly in the lung. CONCLUSIONS NCRT with concurrent S-1/irinotecan produced high response rates and excellent long-term survival, with acceptable adverse effects in patients with rectal cancer. ypN2 is a strong predictor of dismal outcomes, and a combination of ypT and tumor location can identify high-risk patients among those with ypN0/1 disease.
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Affiliation(s)
- Takatoshi Nakamura
- Department of Surgery, Kitasato University School of Medicine, Kanagawa, Japan
| | - Keishi Yamashita
- Department of Surgery, Kitasato University School of Medicine, Kanagawa, Japan
| | - Takeo Sato
- Department of Surgery, Kitasato University School of Medicine, Kanagawa, Japan
| | - Akira Ema
- Department of Surgery, Kitasato University School of Medicine, Kanagawa, Japan
| | - Masanori Naito
- Department of Surgery, Kitasato University School of Medicine, Kanagawa, Japan
| | - Masahiko Watanabe
- Department of Surgery, Kitasato University School of Medicine, Kanagawa, Japan.
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Fokas E, Liersch T, Fietkau R, Hohenberger W, Beissbarth T, Hess C, Becker H, Ghadimi M, Mrak K, Merkel S, Raab HR, Sauer R, Wittekind C, Rödel C. Tumor Regression Grading After Preoperative Chemoradiotherapy for Locally Advanced Rectal Carcinoma Revisited: Updated Results of the CAO/ARO/AIO-94 Trial. J Clin Oncol 2014; 32:1554-62. [DOI: 10.1200/jco.2013.54.3769] [Citation(s) in RCA: 284] [Impact Index Per Article: 25.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Purpose We previously described the prognostic impact of tumor regression grading (TRG) on the outcome of patients with rectal carcinoma treated with preoperative chemoradiotherapy (CRT) in the CAO/ARO/AIO-94 trial. Here we report long-term results after a median follow-up of 132 months. Patients and Methods TRG after preoperative CRT was determined in 386 surgical specimens by the amount of viable tumor cells versus fibrosis, ranging from TRG 4 (no viable tumor cells) to TRG 0 (no signs of regression). Clinicopathologic parameters and TRG were correlated to the cumulative incidence of local recurrence, distant metastasis, and disease-free survival (DFS). Results Ten-year cumulative incidence of distant metastasis and DFS were 10.5% and 89.5% for patients with TRG 4 (complete regression), 29.3% and 73.6% for TRG 2 and 3 (intermediate regression), and 39.6% and 63% for TRG 0 and 1 (poor regression), respectively (P = .005 and P = .008, respectively). On multivariable analysis, residual lymph node metastasis (ypN+) and TRG were the only independent prognostic factors for cumulative incidence of distant metastasis (P < .001 and P = .035, respectively) and DFS (P < .001 and P = .039, respectively), whereas local recurrence was significantly affected by ypN status (P < .001) and lymphatic invasion (P = .026). Conclusion Complete and intermediate tumor regressions were associated with improved long-term outcome in patients with rectal carcinoma after preoperative CRT independent of clinicopathologic parameters. This classification system needs to be prospectively tested in multiple data sets to validate its reproducibility in a wider setting.
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Affiliation(s)
- Emmanouil Fokas
- Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria
| | - Torsten Liersch
- Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria
| | - Rainer Fietkau
- Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria
| | - Werner Hohenberger
- Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria
| | - Tim Beissbarth
- Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria
| | - Clemens Hess
- Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria
| | - Heinz Becker
- Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria
| | - Michael Ghadimi
- Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria
| | - Karl Mrak
- Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria
| | - Susanne Merkel
- Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria
| | - Hans-Rudolf Raab
- Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria
| | - Rolf Sauer
- Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria
| | - Christian Wittekind
- Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria
| | - Claus Rödel
- Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria
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Huang MY, Chen CF, Huang CM, Tsai HL, Yeh YS, Ma CJ, Wu CH, Lu CY, Chai CY, Huang CJ, Wang JY. Helical tomotherapy combined with capecitabine in the preoperative treatment of locally advanced rectal cancer. BIOMED RESEARCH INTERNATIONAL 2014; 2014:352083. [PMID: 24949438 PMCID: PMC4032733 DOI: 10.1155/2014/352083] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/07/2014] [Revised: 04/11/2014] [Accepted: 04/11/2014] [Indexed: 11/18/2022]
Abstract
The aim of this study was to evaluate the efficacy of helical tomotherapy plus capecitabine as a preoperative chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (LARC). Thirty-six LARC patients receiving preoperative CRT were analyzed. Radiotherapy (RT) consisted of 45 Gy to the regional lymph nodes and simultaneous-integrated boost (SIB) 50.4 Gy to the tumor, 5 days/week for 5 weeks. Chemotherapy consisted of capecitabine 850 mg/m(2), twice daily, during the RT days. Patients underwent surgery 6-8 weeks after completion of CRT. Information was collected for patient characteristics, treatment response, and acute and late toxicities. Grade 3/4 (G3+) toxicities occurred in 11.1% of patients (4/36). Sphincter preservation rate was 85.2% (23/27). Five patients (14.3%) achieved pathological complete response. Tumor, nodal, and ypT0-2N0 downstaging were noted in 60% (21/35), 69.6% (16/23), and 57.1% (20/35). Tumor regression grade 2~4 was achieved in 28 patients (80%). After a median follow-up time of 35 months, the most common G3+ late morbidity was ileus and fistula (5.7%, 2/35). The study showed that capecitabine plus helical tomotherapy with an SIB is feasible in treatment of LARC. The treatment modality can achieve a very encouraging sphincter preservation rate and a favorable ypT0-2N0 downstaging rate without excessive toxicity.
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Affiliation(s)
- Ming-Yii Huang
- Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
- Department of Radiation Oncology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
| | - Chin-Fan Chen
- Division of Gastrointestinal and General Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Chun-Ming Huang
- Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
- Department of Radiation Oncology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Hsiang-Lin Tsai
- Division of General Surgery Medicine, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
- School of Medical and Health Sciences, Fooyin University, Kaohsiung 831, Taiwan
| | - Yung-Sung Yeh
- Division of Gastrointestinal and General Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
| | - Cheng-Jen Ma
- Division of Gastrointestinal and General Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
| | - Chan-Han Wu
- School of Medical and Health Sciences, Fooyin University, Kaohsiung 831, Taiwan
- Department of Medical Research, Fooyin University Hospital, Pingtung 928, Taiwan
| | - Chien-Yu Lu
- Department of Internal Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
| | - Chee-Yin Chai
- Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
- Department of Pathology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Chih-Jen Huang
- Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
- Department of Radiation Oncology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
| | - Jaw-Yuan Wang
- Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
- Division of Gastrointestinal and General Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Department of Medical Genetics, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
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21
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O'Connell MJ, Colangelo LH, Beart RW, Petrelli NJ, Allegra CJ, Sharif S, Pitot HC, Shields AF, Landry JC, Ryan DP, Parda DS, Mohiuddin M, Arora A, Evans LS, Bahary N, Soori GS, Eakle J, Robertson JM, Moore DF, Mullane MR, Marchello BT, Ward PJ, Wozniak TF, Roh MS, Yothers G, Wolmark N. Capecitabine and oxaliplatin in the preoperative multimodality treatment of rectal cancer: surgical end points from National Surgical Adjuvant Breast and Bowel Project trial R-04. J Clin Oncol 2014; 32:1927-34. [PMID: 24799484 DOI: 10.1200/jco.2013.53.7753] [Citation(s) in RCA: 326] [Impact Index Per Article: 29.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
PURPOSE The optimal chemotherapy regimen administered concurrently with preoperative radiation therapy (RT) for patients with rectal cancer is unknown. National Surgical Adjuvant Breast and Bowel Project trial R-04 compared four chemotherapy regimens administered concomitantly with RT. PATIENTS AND METHODS Patients with clinical stage II or III rectal cancer who were undergoing preoperative RT (45 Gy in 25 fractions over 5 weeks plus a boost of 5.4 Gy to 10.8 Gy in three to six daily fractions) were randomly assigned to one of the following chemotherapy regimens: continuous intravenous infusional fluorouracil (CVI FU; 225 mg/m(2), 5 days per week), with or without intravenous oxaliplatin (50 mg/m(2) once per week for 5 weeks) or oral capecitabine (825 mg/m(2) twice per day, 5 days per week), with or without oxaliplatin (50 mg/m(2) once per week for 5 weeks). Before random assignment, the surgeon indicated whether the patient was eligible for sphincter-sparing surgery based on clinical staging. The surgical end points were complete pathologic response (pCR), sphincter-sparing surgery, and surgical downstaging (conversion to sphincter-sparing surgery). RESULTS From September 2004 to August 2010, 1,608 patients were randomly assigned. No significant differences in the rates of pCR, sphincter-sparing surgery, or surgical downstaging were identified between the CVI FU and capecitabine regimens or between the two regimens with or without oxaliplatin. Patients treated with oxaliplatin experienced significantly more grade 3 or 4 diarrhea (P < .001). CONCLUSION Administering capecitabine with preoperative RT achieved similar rates of pCR, sphincter-sparing surgery, and surgical downstaging compared with CVI FU. Adding oxaliplatin did not improve surgical outcomes but added significant toxicity. The definitive analysis of local tumor control, disease-free survival, and overall survival will be performed when the protocol-specified number of events has occurred.
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Affiliation(s)
- Michael J O'Connell
- Michael J. O'Connell, Linda H. Colangelo, Robert W. Beart, Nicholas J. Petrelli, Carmen J. Allegra, Saima Sharif, Henry C. Pitot, Anthony F. Shields, David S. Parda, Mohammed Mohiuddin, Amit Arora, Lisa S. Evans, Nathan Bahary, Gamini S. Soori, Janice Eakle, John M. Robertson, Dennis F. Moore Jr, Michael R. Mullane, Benjamin T. Marchello, Patrick J. Ward, Timothy F. Wozniak, Mark S. Roh, Greg Yothers, Norman Wolmark, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; David S. Parda, Norman Wolmark, Allegheny Cancer Center at Allegheny General Hospital; Nathan Bahary, University of Pittsburgh Medical Center and University of Pittsburgh Cancer Institute, Pittsburgh, PA; Robert W. Beart, Colorectal Surgery Institute, Glendale Memorial Hospital, Glendale; Amit Arora, Kaiser Permanente Hayward, Hayward, CA; Nicholas J. Petrelli, Timothy F. Wozniak, Helen F. Graham Cancer Center at Christiana Care Health Service, Newark, DE; Carmen J. Allegra, University of Florida, Gainesville; Janice Eakle, Florida Cancer Specialists, Sarasota; Mark S. Roh, MD Anderson Cancer Center Orlando Health, Orlando, FL; Henry C. Pitot, Mayo Clinic, Rochester, MN; Anthony F. Shields, Karmanos Cancer Institute/Southwest Oncology Group, Detroit; John M. Robertson, Beaumont Hospital System, Royal Oak, MI; Jerome C. Landry, Eastern Cooperative Oncology Group/Emory University, Winship Cancer Institute, Atlanta, GA; David P. Ryan, Massachusetts General Hospital Cancer Center, Boston, MA; Lisa S. Evans, Community Clinical Oncology Program, Southeast CCC Novant Health Derrick L. Davis Forsyth Medical Center, Winston-Salem, NC; Gamini S. Soori, Missouri Valley Cancer Consortium Community Clinical Oncology Program, Omaha, NE; Dennis Moore Jr, Community Clinical Oncology Program, Wichita/St Francis Regional Medical Center/Via Christi Regional Medical Center, Wichita, KS; Michael R. Mullane, Minority-Based Community Clinical Oncology Program John H. Stroger Jr Hospital
| | - Linda H Colangelo
- Michael J. O'Connell, Linda H. Colangelo, Robert W. Beart, Nicholas J. Petrelli, Carmen J. Allegra, Saima Sharif, Henry C. Pitot, Anthony F. Shields, David S. Parda, Mohammed Mohiuddin, Amit Arora, Lisa S. Evans, Nathan Bahary, Gamini S. Soori, Janice Eakle, John M. Robertson, Dennis F. Moore Jr, Michael R. Mullane, Benjamin T. Marchello, Patrick J. Ward, Timothy F. Wozniak, Mark S. Roh, Greg Yothers, Norman Wolmark, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; David S. Parda, Norman Wolmark, Allegheny Cancer Center at Allegheny General Hospital; Nathan Bahary, University of Pittsburgh Medical Center and University of Pittsburgh Cancer Institute, Pittsburgh, PA; Robert W. Beart, Colorectal Surgery Institute, Glendale Memorial Hospital, Glendale; Amit Arora, Kaiser Permanente Hayward, Hayward, CA; Nicholas J. Petrelli, Timothy F. Wozniak, Helen F. Graham Cancer Center at Christiana Care Health Service, Newark, DE; Carmen J. Allegra, University of Florida, Gainesville; Janice Eakle, Florida Cancer Specialists, Sarasota; Mark S. Roh, MD Anderson Cancer Center Orlando Health, Orlando, FL; Henry C. Pitot, Mayo Clinic, Rochester, MN; Anthony F. Shields, Karmanos Cancer Institute/Southwest Oncology Group, Detroit; John M. Robertson, Beaumont Hospital System, Royal Oak, MI; Jerome C. Landry, Eastern Cooperative Oncology Group/Emory University, Winship Cancer Institute, Atlanta, GA; David P. Ryan, Massachusetts General Hospital Cancer Center, Boston, MA; Lisa S. Evans, Community Clinical Oncology Program, Southeast CCC Novant Health Derrick L. Davis Forsyth Medical Center, Winston-Salem, NC; Gamini S. Soori, Missouri Valley Cancer Consortium Community Clinical Oncology Program, Omaha, NE; Dennis Moore Jr, Community Clinical Oncology Program, Wichita/St Francis Regional Medical Center/Via Christi Regional Medical Center, Wichita, KS; Michael R. Mullane, Minority-Based Community Clinical Oncology Program John H. Stroger Jr Hospital
| | - Robert W Beart
- Michael J. O'Connell, Linda H. Colangelo, Robert W. Beart, Nicholas J. Petrelli, Carmen J. Allegra, Saima Sharif, Henry C. Pitot, Anthony F. Shields, David S. Parda, Mohammed Mohiuddin, Amit Arora, Lisa S. Evans, Nathan Bahary, Gamini S. Soori, Janice Eakle, John M. Robertson, Dennis F. Moore Jr, Michael R. Mullane, Benjamin T. Marchello, Patrick J. Ward, Timothy F. Wozniak, Mark S. Roh, Greg Yothers, Norman Wolmark, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; David S. Parda, Norman Wolmark, Allegheny Cancer Center at Allegheny General Hospital; Nathan Bahary, University of Pittsburgh Medical Center and University of Pittsburgh Cancer Institute, Pittsburgh, PA; Robert W. Beart, Colorectal Surgery Institute, Glendale Memorial Hospital, Glendale; Amit Arora, Kaiser Permanente Hayward, Hayward, CA; Nicholas J. Petrelli, Timothy F. Wozniak, Helen F. Graham Cancer Center at Christiana Care Health Service, Newark, DE; Carmen J. Allegra, University of Florida, Gainesville; Janice Eakle, Florida Cancer Specialists, Sarasota; Mark S. Roh, MD Anderson Cancer Center Orlando Health, Orlando, FL; Henry C. Pitot, Mayo Clinic, Rochester, MN; Anthony F. Shields, Karmanos Cancer Institute/Southwest Oncology Group, Detroit; John M. Robertson, Beaumont Hospital System, Royal Oak, MI; Jerome C. Landry, Eastern Cooperative Oncology Group/Emory University, Winship Cancer Institute, Atlanta, GA; David P. Ryan, Massachusetts General Hospital Cancer Center, Boston, MA; Lisa S. Evans, Community Clinical Oncology Program, Southeast CCC Novant Health Derrick L. Davis Forsyth Medical Center, Winston-Salem, NC; Gamini S. Soori, Missouri Valley Cancer Consortium Community Clinical Oncology Program, Omaha, NE; Dennis Moore Jr, Community Clinical Oncology Program, Wichita/St Francis Regional Medical Center/Via Christi Regional Medical Center, Wichita, KS; Michael R. Mullane, Minority-Based Community Clinical Oncology Program John H. Stroger Jr Hospital
| | - Nicholas J Petrelli
- Michael J. O'Connell, Linda H. Colangelo, Robert W. Beart, Nicholas J. Petrelli, Carmen J. Allegra, Saima Sharif, Henry C. Pitot, Anthony F. Shields, David S. Parda, Mohammed Mohiuddin, Amit Arora, Lisa S. Evans, Nathan Bahary, Gamini S. Soori, Janice Eakle, John M. Robertson, Dennis F. Moore Jr, Michael R. Mullane, Benjamin T. Marchello, Patrick J. Ward, Timothy F. Wozniak, Mark S. Roh, Greg Yothers, Norman Wolmark, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; David S. Parda, Norman Wolmark, Allegheny Cancer Center at Allegheny General Hospital; Nathan Bahary, University of Pittsburgh Medical Center and University of Pittsburgh Cancer Institute, Pittsburgh, PA; Robert W. Beart, Colorectal Surgery Institute, Glendale Memorial Hospital, Glendale; Amit Arora, Kaiser Permanente Hayward, Hayward, CA; Nicholas J. Petrelli, Timothy F. Wozniak, Helen F. Graham Cancer Center at Christiana Care Health Service, Newark, DE; Carmen J. Allegra, University of Florida, Gainesville; Janice Eakle, Florida Cancer Specialists, Sarasota; Mark S. Roh, MD Anderson Cancer Center Orlando Health, Orlando, FL; Henry C. Pitot, Mayo Clinic, Rochester, MN; Anthony F. Shields, Karmanos Cancer Institute/Southwest Oncology Group, Detroit; John M. Robertson, Beaumont Hospital System, Royal Oak, MI; Jerome C. Landry, Eastern Cooperative Oncology Group/Emory University, Winship Cancer Institute, Atlanta, GA; David P. Ryan, Massachusetts General Hospital Cancer Center, Boston, MA; Lisa S. Evans, Community Clinical Oncology Program, Southeast CCC Novant Health Derrick L. Davis Forsyth Medical Center, Winston-Salem, NC; Gamini S. Soori, Missouri Valley Cancer Consortium Community Clinical Oncology Program, Omaha, NE; Dennis Moore Jr, Community Clinical Oncology Program, Wichita/St Francis Regional Medical Center/Via Christi Regional Medical Center, Wichita, KS; Michael R. Mullane, Minority-Based Community Clinical Oncology Program John H. Stroger Jr Hospital
| | - Carmen J Allegra
- Michael J. O'Connell, Linda H. Colangelo, Robert W. Beart, Nicholas J. Petrelli, Carmen J. Allegra, Saima Sharif, Henry C. Pitot, Anthony F. Shields, David S. Parda, Mohammed Mohiuddin, Amit Arora, Lisa S. Evans, Nathan Bahary, Gamini S. Soori, Janice Eakle, John M. Robertson, Dennis F. Moore Jr, Michael R. Mullane, Benjamin T. Marchello, Patrick J. Ward, Timothy F. Wozniak, Mark S. Roh, Greg Yothers, Norman Wolmark, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; David S. Parda, Norman Wolmark, Allegheny Cancer Center at Allegheny General Hospital; Nathan Bahary, University of Pittsburgh Medical Center and University of Pittsburgh Cancer Institute, Pittsburgh, PA; Robert W. Beart, Colorectal Surgery Institute, Glendale Memorial Hospital, Glendale; Amit Arora, Kaiser Permanente Hayward, Hayward, CA; Nicholas J. Petrelli, Timothy F. Wozniak, Helen F. Graham Cancer Center at Christiana Care Health Service, Newark, DE; Carmen J. Allegra, University of Florida, Gainesville; Janice Eakle, Florida Cancer Specialists, Sarasota; Mark S. Roh, MD Anderson Cancer Center Orlando Health, Orlando, FL; Henry C. Pitot, Mayo Clinic, Rochester, MN; Anthony F. Shields, Karmanos Cancer Institute/Southwest Oncology Group, Detroit; John M. Robertson, Beaumont Hospital System, Royal Oak, MI; Jerome C. Landry, Eastern Cooperative Oncology Group/Emory University, Winship Cancer Institute, Atlanta, GA; David P. Ryan, Massachusetts General Hospital Cancer Center, Boston, MA; Lisa S. Evans, Community Clinical Oncology Program, Southeast CCC Novant Health Derrick L. Davis Forsyth Medical Center, Winston-Salem, NC; Gamini S. Soori, Missouri Valley Cancer Consortium Community Clinical Oncology Program, Omaha, NE; Dennis Moore Jr, Community Clinical Oncology Program, Wichita/St Francis Regional Medical Center/Via Christi Regional Medical Center, Wichita, KS; Michael R. Mullane, Minority-Based Community Clinical Oncology Program John H. Stroger Jr Hospital
| | - Saima Sharif
- Michael J. O'Connell, Linda H. Colangelo, Robert W. Beart, Nicholas J. Petrelli, Carmen J. Allegra, Saima Sharif, Henry C. Pitot, Anthony F. Shields, David S. Parda, Mohammed Mohiuddin, Amit Arora, Lisa S. Evans, Nathan Bahary, Gamini S. Soori, Janice Eakle, John M. Robertson, Dennis F. Moore Jr, Michael R. Mullane, Benjamin T. Marchello, Patrick J. Ward, Timothy F. Wozniak, Mark S. Roh, Greg Yothers, Norman Wolmark, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; David S. Parda, Norman Wolmark, Allegheny Cancer Center at Allegheny General Hospital; Nathan Bahary, University of Pittsburgh Medical Center and University of Pittsburgh Cancer Institute, Pittsburgh, PA; Robert W. Beart, Colorectal Surgery Institute, Glendale Memorial Hospital, Glendale; Amit Arora, Kaiser Permanente Hayward, Hayward, CA; Nicholas J. Petrelli, Timothy F. Wozniak, Helen F. Graham Cancer Center at Christiana Care Health Service, Newark, DE; Carmen J. Allegra, University of Florida, Gainesville; Janice Eakle, Florida Cancer Specialists, Sarasota; Mark S. Roh, MD Anderson Cancer Center Orlando Health, Orlando, FL; Henry C. Pitot, Mayo Clinic, Rochester, MN; Anthony F. Shields, Karmanos Cancer Institute/Southwest Oncology Group, Detroit; John M. Robertson, Beaumont Hospital System, Royal Oak, MI; Jerome C. Landry, Eastern Cooperative Oncology Group/Emory University, Winship Cancer Institute, Atlanta, GA; David P. Ryan, Massachusetts General Hospital Cancer Center, Boston, MA; Lisa S. Evans, Community Clinical Oncology Program, Southeast CCC Novant Health Derrick L. Davis Forsyth Medical Center, Winston-Salem, NC; Gamini S. Soori, Missouri Valley Cancer Consortium Community Clinical Oncology Program, Omaha, NE; Dennis Moore Jr, Community Clinical Oncology Program, Wichita/St Francis Regional Medical Center/Via Christi Regional Medical Center, Wichita, KS; Michael R. Mullane, Minority-Based Community Clinical Oncology Program John H. Stroger Jr Hospital
| | - Henry C Pitot
- Michael J. O'Connell, Linda H. Colangelo, Robert W. Beart, Nicholas J. Petrelli, Carmen J. Allegra, Saima Sharif, Henry C. Pitot, Anthony F. Shields, David S. Parda, Mohammed Mohiuddin, Amit Arora, Lisa S. Evans, Nathan Bahary, Gamini S. Soori, Janice Eakle, John M. Robertson, Dennis F. Moore Jr, Michael R. Mullane, Benjamin T. Marchello, Patrick J. Ward, Timothy F. Wozniak, Mark S. Roh, Greg Yothers, Norman Wolmark, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; David S. Parda, Norman Wolmark, Allegheny Cancer Center at Allegheny General Hospital; Nathan Bahary, University of Pittsburgh Medical Center and University of Pittsburgh Cancer Institute, Pittsburgh, PA; Robert W. Beart, Colorectal Surgery Institute, Glendale Memorial Hospital, Glendale; Amit Arora, Kaiser Permanente Hayward, Hayward, CA; Nicholas J. Petrelli, Timothy F. Wozniak, Helen F. Graham Cancer Center at Christiana Care Health Service, Newark, DE; Carmen J. Allegra, University of Florida, Gainesville; Janice Eakle, Florida Cancer Specialists, Sarasota; Mark S. Roh, MD Anderson Cancer Center Orlando Health, Orlando, FL; Henry C. Pitot, Mayo Clinic, Rochester, MN; Anthony F. Shields, Karmanos Cancer Institute/Southwest Oncology Group, Detroit; John M. Robertson, Beaumont Hospital System, Royal Oak, MI; Jerome C. Landry, Eastern Cooperative Oncology Group/Emory University, Winship Cancer Institute, Atlanta, GA; David P. Ryan, Massachusetts General Hospital Cancer Center, Boston, MA; Lisa S. Evans, Community Clinical Oncology Program, Southeast CCC Novant Health Derrick L. Davis Forsyth Medical Center, Winston-Salem, NC; Gamini S. Soori, Missouri Valley Cancer Consortium Community Clinical Oncology Program, Omaha, NE; Dennis Moore Jr, Community Clinical Oncology Program, Wichita/St Francis Regional Medical Center/Via Christi Regional Medical Center, Wichita, KS; Michael R. Mullane, Minority-Based Community Clinical Oncology Program John H. Stroger Jr Hospital
| | - Anthony F Shields
- Michael J. O'Connell, Linda H. Colangelo, Robert W. Beart, Nicholas J. Petrelli, Carmen J. Allegra, Saima Sharif, Henry C. Pitot, Anthony F. Shields, David S. Parda, Mohammed Mohiuddin, Amit Arora, Lisa S. Evans, Nathan Bahary, Gamini S. Soori, Janice Eakle, John M. Robertson, Dennis F. Moore Jr, Michael R. Mullane, Benjamin T. Marchello, Patrick J. Ward, Timothy F. Wozniak, Mark S. Roh, Greg Yothers, Norman Wolmark, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; David S. Parda, Norman Wolmark, Allegheny Cancer Center at Allegheny General Hospital; Nathan Bahary, University of Pittsburgh Medical Center and University of Pittsburgh Cancer Institute, Pittsburgh, PA; Robert W. Beart, Colorectal Surgery Institute, Glendale Memorial Hospital, Glendale; Amit Arora, Kaiser Permanente Hayward, Hayward, CA; Nicholas J. Petrelli, Timothy F. Wozniak, Helen F. Graham Cancer Center at Christiana Care Health Service, Newark, DE; Carmen J. Allegra, University of Florida, Gainesville; Janice Eakle, Florida Cancer Specialists, Sarasota; Mark S. Roh, MD Anderson Cancer Center Orlando Health, Orlando, FL; Henry C. Pitot, Mayo Clinic, Rochester, MN; Anthony F. Shields, Karmanos Cancer Institute/Southwest Oncology Group, Detroit; John M. Robertson, Beaumont Hospital System, Royal Oak, MI; Jerome C. Landry, Eastern Cooperative Oncology Group/Emory University, Winship Cancer Institute, Atlanta, GA; David P. Ryan, Massachusetts General Hospital Cancer Center, Boston, MA; Lisa S. Evans, Community Clinical Oncology Program, Southeast CCC Novant Health Derrick L. Davis Forsyth Medical Center, Winston-Salem, NC; Gamini S. Soori, Missouri Valley Cancer Consortium Community Clinical Oncology Program, Omaha, NE; Dennis Moore Jr, Community Clinical Oncology Program, Wichita/St Francis Regional Medical Center/Via Christi Regional Medical Center, Wichita, KS; Michael R. Mullane, Minority-Based Community Clinical Oncology Program John H. Stroger Jr Hospital
| | - Jerome C Landry
- Michael J. O'Connell, Linda H. Colangelo, Robert W. Beart, Nicholas J. Petrelli, Carmen J. Allegra, Saima Sharif, Henry C. Pitot, Anthony F. Shields, David S. Parda, Mohammed Mohiuddin, Amit Arora, Lisa S. Evans, Nathan Bahary, Gamini S. Soori, Janice Eakle, John M. Robertson, Dennis F. Moore Jr, Michael R. Mullane, Benjamin T. Marchello, Patrick J. Ward, Timothy F. Wozniak, Mark S. Roh, Greg Yothers, Norman Wolmark, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; David S. Parda, Norman Wolmark, Allegheny Cancer Center at Allegheny General Hospital; Nathan Bahary, University of Pittsburgh Medical Center and University of Pittsburgh Cancer Institute, Pittsburgh, PA; Robert W. Beart, Colorectal Surgery Institute, Glendale Memorial Hospital, Glendale; Amit Arora, Kaiser Permanente Hayward, Hayward, CA; Nicholas J. Petrelli, Timothy F. Wozniak, Helen F. Graham Cancer Center at Christiana Care Health Service, Newark, DE; Carmen J. Allegra, University of Florida, Gainesville; Janice Eakle, Florida Cancer Specialists, Sarasota; Mark S. Roh, MD Anderson Cancer Center Orlando Health, Orlando, FL; Henry C. Pitot, Mayo Clinic, Rochester, MN; Anthony F. Shields, Karmanos Cancer Institute/Southwest Oncology Group, Detroit; John M. Robertson, Beaumont Hospital System, Royal Oak, MI; Jerome C. Landry, Eastern Cooperative Oncology Group/Emory University, Winship Cancer Institute, Atlanta, GA; David P. Ryan, Massachusetts General Hospital Cancer Center, Boston, MA; Lisa S. Evans, Community Clinical Oncology Program, Southeast CCC Novant Health Derrick L. Davis Forsyth Medical Center, Winston-Salem, NC; Gamini S. Soori, Missouri Valley Cancer Consortium Community Clinical Oncology Program, Omaha, NE; Dennis Moore Jr, Community Clinical Oncology Program, Wichita/St Francis Regional Medical Center/Via Christi Regional Medical Center, Wichita, KS; Michael R. Mullane, Minority-Based Community Clinical Oncology Program John H. Stroger Jr Hospital
| | - David P Ryan
- Michael J. O'Connell, Linda H. Colangelo, Robert W. Beart, Nicholas J. Petrelli, Carmen J. Allegra, Saima Sharif, Henry C. Pitot, Anthony F. Shields, David S. Parda, Mohammed Mohiuddin, Amit Arora, Lisa S. Evans, Nathan Bahary, Gamini S. Soori, Janice Eakle, John M. Robertson, Dennis F. Moore Jr, Michael R. Mullane, Benjamin T. Marchello, Patrick J. Ward, Timothy F. Wozniak, Mark S. Roh, Greg Yothers, Norman Wolmark, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; David S. Parda, Norman Wolmark, Allegheny Cancer Center at Allegheny General Hospital; Nathan Bahary, University of Pittsburgh Medical Center and University of Pittsburgh Cancer Institute, Pittsburgh, PA; Robert W. Beart, Colorectal Surgery Institute, Glendale Memorial Hospital, Glendale; Amit Arora, Kaiser Permanente Hayward, Hayward, CA; Nicholas J. Petrelli, Timothy F. Wozniak, Helen F. Graham Cancer Center at Christiana Care Health Service, Newark, DE; Carmen J. Allegra, University of Florida, Gainesville; Janice Eakle, Florida Cancer Specialists, Sarasota; Mark S. Roh, MD Anderson Cancer Center Orlando Health, Orlando, FL; Henry C. Pitot, Mayo Clinic, Rochester, MN; Anthony F. Shields, Karmanos Cancer Institute/Southwest Oncology Group, Detroit; John M. Robertson, Beaumont Hospital System, Royal Oak, MI; Jerome C. Landry, Eastern Cooperative Oncology Group/Emory University, Winship Cancer Institute, Atlanta, GA; David P. Ryan, Massachusetts General Hospital Cancer Center, Boston, MA; Lisa S. Evans, Community Clinical Oncology Program, Southeast CCC Novant Health Derrick L. Davis Forsyth Medical Center, Winston-Salem, NC; Gamini S. Soori, Missouri Valley Cancer Consortium Community Clinical Oncology Program, Omaha, NE; Dennis Moore Jr, Community Clinical Oncology Program, Wichita/St Francis Regional Medical Center/Via Christi Regional Medical Center, Wichita, KS; Michael R. Mullane, Minority-Based Community Clinical Oncology Program John H. Stroger Jr Hospital
| | - David S Parda
- Michael J. O'Connell, Linda H. Colangelo, Robert W. Beart, Nicholas J. Petrelli, Carmen J. Allegra, Saima Sharif, Henry C. Pitot, Anthony F. Shields, David S. Parda, Mohammed Mohiuddin, Amit Arora, Lisa S. Evans, Nathan Bahary, Gamini S. Soori, Janice Eakle, John M. Robertson, Dennis F. Moore Jr, Michael R. Mullane, Benjamin T. Marchello, Patrick J. Ward, Timothy F. Wozniak, Mark S. Roh, Greg Yothers, Norman Wolmark, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; David S. Parda, Norman Wolmark, Allegheny Cancer Center at Allegheny General Hospital; Nathan Bahary, University of Pittsburgh Medical Center and University of Pittsburgh Cancer Institute, Pittsburgh, PA; Robert W. Beart, Colorectal Surgery Institute, Glendale Memorial Hospital, Glendale; Amit Arora, Kaiser Permanente Hayward, Hayward, CA; Nicholas J. Petrelli, Timothy F. Wozniak, Helen F. Graham Cancer Center at Christiana Care Health Service, Newark, DE; Carmen J. Allegra, University of Florida, Gainesville; Janice Eakle, Florida Cancer Specialists, Sarasota; Mark S. Roh, MD Anderson Cancer Center Orlando Health, Orlando, FL; Henry C. Pitot, Mayo Clinic, Rochester, MN; Anthony F. Shields, Karmanos Cancer Institute/Southwest Oncology Group, Detroit; John M. Robertson, Beaumont Hospital System, Royal Oak, MI; Jerome C. Landry, Eastern Cooperative Oncology Group/Emory University, Winship Cancer Institute, Atlanta, GA; David P. Ryan, Massachusetts General Hospital Cancer Center, Boston, MA; Lisa S. Evans, Community Clinical Oncology Program, Southeast CCC Novant Health Derrick L. Davis Forsyth Medical Center, Winston-Salem, NC; Gamini S. Soori, Missouri Valley Cancer Consortium Community Clinical Oncology Program, Omaha, NE; Dennis Moore Jr, Community Clinical Oncology Program, Wichita/St Francis Regional Medical Center/Via Christi Regional Medical Center, Wichita, KS; Michael R. Mullane, Minority-Based Community Clinical Oncology Program John H. Stroger Jr Hospital
| | - Mohammed Mohiuddin
- Michael J. O'Connell, Linda H. Colangelo, Robert W. Beart, Nicholas J. Petrelli, Carmen J. Allegra, Saima Sharif, Henry C. Pitot, Anthony F. Shields, David S. Parda, Mohammed Mohiuddin, Amit Arora, Lisa S. Evans, Nathan Bahary, Gamini S. Soori, Janice Eakle, John M. Robertson, Dennis F. Moore Jr, Michael R. Mullane, Benjamin T. Marchello, Patrick J. Ward, Timothy F. Wozniak, Mark S. Roh, Greg Yothers, Norman Wolmark, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; David S. Parda, Norman Wolmark, Allegheny Cancer Center at Allegheny General Hospital; Nathan Bahary, University of Pittsburgh Medical Center and University of Pittsburgh Cancer Institute, Pittsburgh, PA; Robert W. Beart, Colorectal Surgery Institute, Glendale Memorial Hospital, Glendale; Amit Arora, Kaiser Permanente Hayward, Hayward, CA; Nicholas J. Petrelli, Timothy F. Wozniak, Helen F. Graham Cancer Center at Christiana Care Health Service, Newark, DE; Carmen J. Allegra, University of Florida, Gainesville; Janice Eakle, Florida Cancer Specialists, Sarasota; Mark S. Roh, MD Anderson Cancer Center Orlando Health, Orlando, FL; Henry C. Pitot, Mayo Clinic, Rochester, MN; Anthony F. Shields, Karmanos Cancer Institute/Southwest Oncology Group, Detroit; John M. Robertson, Beaumont Hospital System, Royal Oak, MI; Jerome C. Landry, Eastern Cooperative Oncology Group/Emory University, Winship Cancer Institute, Atlanta, GA; David P. Ryan, Massachusetts General Hospital Cancer Center, Boston, MA; Lisa S. Evans, Community Clinical Oncology Program, Southeast CCC Novant Health Derrick L. Davis Forsyth Medical Center, Winston-Salem, NC; Gamini S. Soori, Missouri Valley Cancer Consortium Community Clinical Oncology Program, Omaha, NE; Dennis Moore Jr, Community Clinical Oncology Program, Wichita/St Francis Regional Medical Center/Via Christi Regional Medical Center, Wichita, KS; Michael R. Mullane, Minority-Based Community Clinical Oncology Program John H. Stroger Jr Hospital
| | - Amit Arora
- Michael J. O'Connell, Linda H. Colangelo, Robert W. Beart, Nicholas J. Petrelli, Carmen J. Allegra, Saima Sharif, Henry C. Pitot, Anthony F. Shields, David S. Parda, Mohammed Mohiuddin, Amit Arora, Lisa S. Evans, Nathan Bahary, Gamini S. Soori, Janice Eakle, John M. Robertson, Dennis F. Moore Jr, Michael R. Mullane, Benjamin T. Marchello, Patrick J. Ward, Timothy F. Wozniak, Mark S. Roh, Greg Yothers, Norman Wolmark, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; David S. Parda, Norman Wolmark, Allegheny Cancer Center at Allegheny General Hospital; Nathan Bahary, University of Pittsburgh Medical Center and University of Pittsburgh Cancer Institute, Pittsburgh, PA; Robert W. Beart, Colorectal Surgery Institute, Glendale Memorial Hospital, Glendale; Amit Arora, Kaiser Permanente Hayward, Hayward, CA; Nicholas J. Petrelli, Timothy F. Wozniak, Helen F. Graham Cancer Center at Christiana Care Health Service, Newark, DE; Carmen J. Allegra, University of Florida, Gainesville; Janice Eakle, Florida Cancer Specialists, Sarasota; Mark S. Roh, MD Anderson Cancer Center Orlando Health, Orlando, FL; Henry C. Pitot, Mayo Clinic, Rochester, MN; Anthony F. Shields, Karmanos Cancer Institute/Southwest Oncology Group, Detroit; John M. Robertson, Beaumont Hospital System, Royal Oak, MI; Jerome C. Landry, Eastern Cooperative Oncology Group/Emory University, Winship Cancer Institute, Atlanta, GA; David P. Ryan, Massachusetts General Hospital Cancer Center, Boston, MA; Lisa S. Evans, Community Clinical Oncology Program, Southeast CCC Novant Health Derrick L. Davis Forsyth Medical Center, Winston-Salem, NC; Gamini S. Soori, Missouri Valley Cancer Consortium Community Clinical Oncology Program, Omaha, NE; Dennis Moore Jr, Community Clinical Oncology Program, Wichita/St Francis Regional Medical Center/Via Christi Regional Medical Center, Wichita, KS; Michael R. Mullane, Minority-Based Community Clinical Oncology Program John H. Stroger Jr Hospital
| | - Lisa S Evans
- Michael J. O'Connell, Linda H. Colangelo, Robert W. Beart, Nicholas J. Petrelli, Carmen J. Allegra, Saima Sharif, Henry C. Pitot, Anthony F. Shields, David S. Parda, Mohammed Mohiuddin, Amit Arora, Lisa S. Evans, Nathan Bahary, Gamini S. Soori, Janice Eakle, John M. Robertson, Dennis F. Moore Jr, Michael R. Mullane, Benjamin T. Marchello, Patrick J. Ward, Timothy F. Wozniak, Mark S. Roh, Greg Yothers, Norman Wolmark, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; David S. Parda, Norman Wolmark, Allegheny Cancer Center at Allegheny General Hospital; Nathan Bahary, University of Pittsburgh Medical Center and University of Pittsburgh Cancer Institute, Pittsburgh, PA; Robert W. Beart, Colorectal Surgery Institute, Glendale Memorial Hospital, Glendale; Amit Arora, Kaiser Permanente Hayward, Hayward, CA; Nicholas J. Petrelli, Timothy F. Wozniak, Helen F. Graham Cancer Center at Christiana Care Health Service, Newark, DE; Carmen J. Allegra, University of Florida, Gainesville; Janice Eakle, Florida Cancer Specialists, Sarasota; Mark S. Roh, MD Anderson Cancer Center Orlando Health, Orlando, FL; Henry C. Pitot, Mayo Clinic, Rochester, MN; Anthony F. Shields, Karmanos Cancer Institute/Southwest Oncology Group, Detroit; John M. Robertson, Beaumont Hospital System, Royal Oak, MI; Jerome C. Landry, Eastern Cooperative Oncology Group/Emory University, Winship Cancer Institute, Atlanta, GA; David P. Ryan, Massachusetts General Hospital Cancer Center, Boston, MA; Lisa S. Evans, Community Clinical Oncology Program, Southeast CCC Novant Health Derrick L. Davis Forsyth Medical Center, Winston-Salem, NC; Gamini S. Soori, Missouri Valley Cancer Consortium Community Clinical Oncology Program, Omaha, NE; Dennis Moore Jr, Community Clinical Oncology Program, Wichita/St Francis Regional Medical Center/Via Christi Regional Medical Center, Wichita, KS; Michael R. Mullane, Minority-Based Community Clinical Oncology Program John H. Stroger Jr Hospital
| | - Nathan Bahary
- Michael J. O'Connell, Linda H. Colangelo, Robert W. Beart, Nicholas J. Petrelli, Carmen J. Allegra, Saima Sharif, Henry C. Pitot, Anthony F. Shields, David S. Parda, Mohammed Mohiuddin, Amit Arora, Lisa S. Evans, Nathan Bahary, Gamini S. Soori, Janice Eakle, John M. Robertson, Dennis F. Moore Jr, Michael R. Mullane, Benjamin T. Marchello, Patrick J. Ward, Timothy F. Wozniak, Mark S. Roh, Greg Yothers, Norman Wolmark, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; David S. Parda, Norman Wolmark, Allegheny Cancer Center at Allegheny General Hospital; Nathan Bahary, University of Pittsburgh Medical Center and University of Pittsburgh Cancer Institute, Pittsburgh, PA; Robert W. Beart, Colorectal Surgery Institute, Glendale Memorial Hospital, Glendale; Amit Arora, Kaiser Permanente Hayward, Hayward, CA; Nicholas J. Petrelli, Timothy F. Wozniak, Helen F. Graham Cancer Center at Christiana Care Health Service, Newark, DE; Carmen J. Allegra, University of Florida, Gainesville; Janice Eakle, Florida Cancer Specialists, Sarasota; Mark S. Roh, MD Anderson Cancer Center Orlando Health, Orlando, FL; Henry C. Pitot, Mayo Clinic, Rochester, MN; Anthony F. Shields, Karmanos Cancer Institute/Southwest Oncology Group, Detroit; John M. Robertson, Beaumont Hospital System, Royal Oak, MI; Jerome C. Landry, Eastern Cooperative Oncology Group/Emory University, Winship Cancer Institute, Atlanta, GA; David P. Ryan, Massachusetts General Hospital Cancer Center, Boston, MA; Lisa S. Evans, Community Clinical Oncology Program, Southeast CCC Novant Health Derrick L. Davis Forsyth Medical Center, Winston-Salem, NC; Gamini S. Soori, Missouri Valley Cancer Consortium Community Clinical Oncology Program, Omaha, NE; Dennis Moore Jr, Community Clinical Oncology Program, Wichita/St Francis Regional Medical Center/Via Christi Regional Medical Center, Wichita, KS; Michael R. Mullane, Minority-Based Community Clinical Oncology Program John H. Stroger Jr Hospital
| | - Gamini S Soori
- Michael J. O'Connell, Linda H. Colangelo, Robert W. Beart, Nicholas J. Petrelli, Carmen J. Allegra, Saima Sharif, Henry C. Pitot, Anthony F. Shields, David S. Parda, Mohammed Mohiuddin, Amit Arora, Lisa S. Evans, Nathan Bahary, Gamini S. Soori, Janice Eakle, John M. Robertson, Dennis F. Moore Jr, Michael R. Mullane, Benjamin T. Marchello, Patrick J. Ward, Timothy F. Wozniak, Mark S. Roh, Greg Yothers, Norman Wolmark, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; David S. Parda, Norman Wolmark, Allegheny Cancer Center at Allegheny General Hospital; Nathan Bahary, University of Pittsburgh Medical Center and University of Pittsburgh Cancer Institute, Pittsburgh, PA; Robert W. Beart, Colorectal Surgery Institute, Glendale Memorial Hospital, Glendale; Amit Arora, Kaiser Permanente Hayward, Hayward, CA; Nicholas J. Petrelli, Timothy F. Wozniak, Helen F. Graham Cancer Center at Christiana Care Health Service, Newark, DE; Carmen J. Allegra, University of Florida, Gainesville; Janice Eakle, Florida Cancer Specialists, Sarasota; Mark S. Roh, MD Anderson Cancer Center Orlando Health, Orlando, FL; Henry C. Pitot, Mayo Clinic, Rochester, MN; Anthony F. Shields, Karmanos Cancer Institute/Southwest Oncology Group, Detroit; John M. Robertson, Beaumont Hospital System, Royal Oak, MI; Jerome C. Landry, Eastern Cooperative Oncology Group/Emory University, Winship Cancer Institute, Atlanta, GA; David P. Ryan, Massachusetts General Hospital Cancer Center, Boston, MA; Lisa S. Evans, Community Clinical Oncology Program, Southeast CCC Novant Health Derrick L. Davis Forsyth Medical Center, Winston-Salem, NC; Gamini S. Soori, Missouri Valley Cancer Consortium Community Clinical Oncology Program, Omaha, NE; Dennis Moore Jr, Community Clinical Oncology Program, Wichita/St Francis Regional Medical Center/Via Christi Regional Medical Center, Wichita, KS; Michael R. Mullane, Minority-Based Community Clinical Oncology Program John H. Stroger Jr Hospital
| | - Janice Eakle
- Michael J. O'Connell, Linda H. Colangelo, Robert W. Beart, Nicholas J. Petrelli, Carmen J. Allegra, Saima Sharif, Henry C. Pitot, Anthony F. Shields, David S. Parda, Mohammed Mohiuddin, Amit Arora, Lisa S. Evans, Nathan Bahary, Gamini S. Soori, Janice Eakle, John M. Robertson, Dennis F. Moore Jr, Michael R. Mullane, Benjamin T. Marchello, Patrick J. Ward, Timothy F. Wozniak, Mark S. Roh, Greg Yothers, Norman Wolmark, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; David S. Parda, Norman Wolmark, Allegheny Cancer Center at Allegheny General Hospital; Nathan Bahary, University of Pittsburgh Medical Center and University of Pittsburgh Cancer Institute, Pittsburgh, PA; Robert W. Beart, Colorectal Surgery Institute, Glendale Memorial Hospital, Glendale; Amit Arora, Kaiser Permanente Hayward, Hayward, CA; Nicholas J. Petrelli, Timothy F. Wozniak, Helen F. Graham Cancer Center at Christiana Care Health Service, Newark, DE; Carmen J. Allegra, University of Florida, Gainesville; Janice Eakle, Florida Cancer Specialists, Sarasota; Mark S. Roh, MD Anderson Cancer Center Orlando Health, Orlando, FL; Henry C. Pitot, Mayo Clinic, Rochester, MN; Anthony F. Shields, Karmanos Cancer Institute/Southwest Oncology Group, Detroit; John M. Robertson, Beaumont Hospital System, Royal Oak, MI; Jerome C. Landry, Eastern Cooperative Oncology Group/Emory University, Winship Cancer Institute, Atlanta, GA; David P. Ryan, Massachusetts General Hospital Cancer Center, Boston, MA; Lisa S. Evans, Community Clinical Oncology Program, Southeast CCC Novant Health Derrick L. Davis Forsyth Medical Center, Winston-Salem, NC; Gamini S. Soori, Missouri Valley Cancer Consortium Community Clinical Oncology Program, Omaha, NE; Dennis Moore Jr, Community Clinical Oncology Program, Wichita/St Francis Regional Medical Center/Via Christi Regional Medical Center, Wichita, KS; Michael R. Mullane, Minority-Based Community Clinical Oncology Program John H. Stroger Jr Hospital
| | - John M Robertson
- Michael J. O'Connell, Linda H. Colangelo, Robert W. Beart, Nicholas J. Petrelli, Carmen J. Allegra, Saima Sharif, Henry C. Pitot, Anthony F. Shields, David S. Parda, Mohammed Mohiuddin, Amit Arora, Lisa S. Evans, Nathan Bahary, Gamini S. Soori, Janice Eakle, John M. Robertson, Dennis F. Moore Jr, Michael R. Mullane, Benjamin T. Marchello, Patrick J. Ward, Timothy F. Wozniak, Mark S. Roh, Greg Yothers, Norman Wolmark, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; David S. Parda, Norman Wolmark, Allegheny Cancer Center at Allegheny General Hospital; Nathan Bahary, University of Pittsburgh Medical Center and University of Pittsburgh Cancer Institute, Pittsburgh, PA; Robert W. Beart, Colorectal Surgery Institute, Glendale Memorial Hospital, Glendale; Amit Arora, Kaiser Permanente Hayward, Hayward, CA; Nicholas J. Petrelli, Timothy F. Wozniak, Helen F. Graham Cancer Center at Christiana Care Health Service, Newark, DE; Carmen J. Allegra, University of Florida, Gainesville; Janice Eakle, Florida Cancer Specialists, Sarasota; Mark S. Roh, MD Anderson Cancer Center Orlando Health, Orlando, FL; Henry C. Pitot, Mayo Clinic, Rochester, MN; Anthony F. Shields, Karmanos Cancer Institute/Southwest Oncology Group, Detroit; John M. Robertson, Beaumont Hospital System, Royal Oak, MI; Jerome C. Landry, Eastern Cooperative Oncology Group/Emory University, Winship Cancer Institute, Atlanta, GA; David P. Ryan, Massachusetts General Hospital Cancer Center, Boston, MA; Lisa S. Evans, Community Clinical Oncology Program, Southeast CCC Novant Health Derrick L. Davis Forsyth Medical Center, Winston-Salem, NC; Gamini S. Soori, Missouri Valley Cancer Consortium Community Clinical Oncology Program, Omaha, NE; Dennis Moore Jr, Community Clinical Oncology Program, Wichita/St Francis Regional Medical Center/Via Christi Regional Medical Center, Wichita, KS; Michael R. Mullane, Minority-Based Community Clinical Oncology Program John H. Stroger Jr Hospital
| | - Dennis F Moore
- Michael J. O'Connell, Linda H. Colangelo, Robert W. Beart, Nicholas J. Petrelli, Carmen J. Allegra, Saima Sharif, Henry C. Pitot, Anthony F. Shields, David S. Parda, Mohammed Mohiuddin, Amit Arora, Lisa S. Evans, Nathan Bahary, Gamini S. Soori, Janice Eakle, John M. Robertson, Dennis F. Moore Jr, Michael R. Mullane, Benjamin T. Marchello, Patrick J. Ward, Timothy F. Wozniak, Mark S. Roh, Greg Yothers, Norman Wolmark, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; David S. Parda, Norman Wolmark, Allegheny Cancer Center at Allegheny General Hospital; Nathan Bahary, University of Pittsburgh Medical Center and University of Pittsburgh Cancer Institute, Pittsburgh, PA; Robert W. Beart, Colorectal Surgery Institute, Glendale Memorial Hospital, Glendale; Amit Arora, Kaiser Permanente Hayward, Hayward, CA; Nicholas J. Petrelli, Timothy F. Wozniak, Helen F. Graham Cancer Center at Christiana Care Health Service, Newark, DE; Carmen J. Allegra, University of Florida, Gainesville; Janice Eakle, Florida Cancer Specialists, Sarasota; Mark S. Roh, MD Anderson Cancer Center Orlando Health, Orlando, FL; Henry C. Pitot, Mayo Clinic, Rochester, MN; Anthony F. Shields, Karmanos Cancer Institute/Southwest Oncology Group, Detroit; John M. Robertson, Beaumont Hospital System, Royal Oak, MI; Jerome C. Landry, Eastern Cooperative Oncology Group/Emory University, Winship Cancer Institute, Atlanta, GA; David P. Ryan, Massachusetts General Hospital Cancer Center, Boston, MA; Lisa S. Evans, Community Clinical Oncology Program, Southeast CCC Novant Health Derrick L. Davis Forsyth Medical Center, Winston-Salem, NC; Gamini S. Soori, Missouri Valley Cancer Consortium Community Clinical Oncology Program, Omaha, NE; Dennis Moore Jr, Community Clinical Oncology Program, Wichita/St Francis Regional Medical Center/Via Christi Regional Medical Center, Wichita, KS; Michael R. Mullane, Minority-Based Community Clinical Oncology Program John H. Stroger Jr Hospital
| | - Michael R Mullane
- Michael J. O'Connell, Linda H. Colangelo, Robert W. Beart, Nicholas J. Petrelli, Carmen J. Allegra, Saima Sharif, Henry C. Pitot, Anthony F. Shields, David S. Parda, Mohammed Mohiuddin, Amit Arora, Lisa S. Evans, Nathan Bahary, Gamini S. Soori, Janice Eakle, John M. Robertson, Dennis F. Moore Jr, Michael R. Mullane, Benjamin T. Marchello, Patrick J. Ward, Timothy F. Wozniak, Mark S. Roh, Greg Yothers, Norman Wolmark, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; David S. Parda, Norman Wolmark, Allegheny Cancer Center at Allegheny General Hospital; Nathan Bahary, University of Pittsburgh Medical Center and University of Pittsburgh Cancer Institute, Pittsburgh, PA; Robert W. Beart, Colorectal Surgery Institute, Glendale Memorial Hospital, Glendale; Amit Arora, Kaiser Permanente Hayward, Hayward, CA; Nicholas J. Petrelli, Timothy F. Wozniak, Helen F. Graham Cancer Center at Christiana Care Health Service, Newark, DE; Carmen J. Allegra, University of Florida, Gainesville; Janice Eakle, Florida Cancer Specialists, Sarasota; Mark S. Roh, MD Anderson Cancer Center Orlando Health, Orlando, FL; Henry C. Pitot, Mayo Clinic, Rochester, MN; Anthony F. Shields, Karmanos Cancer Institute/Southwest Oncology Group, Detroit; John M. Robertson, Beaumont Hospital System, Royal Oak, MI; Jerome C. Landry, Eastern Cooperative Oncology Group/Emory University, Winship Cancer Institute, Atlanta, GA; David P. Ryan, Massachusetts General Hospital Cancer Center, Boston, MA; Lisa S. Evans, Community Clinical Oncology Program, Southeast CCC Novant Health Derrick L. Davis Forsyth Medical Center, Winston-Salem, NC; Gamini S. Soori, Missouri Valley Cancer Consortium Community Clinical Oncology Program, Omaha, NE; Dennis Moore Jr, Community Clinical Oncology Program, Wichita/St Francis Regional Medical Center/Via Christi Regional Medical Center, Wichita, KS; Michael R. Mullane, Minority-Based Community Clinical Oncology Program John H. Stroger Jr Hospital
| | - Benjamin T Marchello
- Michael J. O'Connell, Linda H. Colangelo, Robert W. Beart, Nicholas J. Petrelli, Carmen J. Allegra, Saima Sharif, Henry C. Pitot, Anthony F. Shields, David S. Parda, Mohammed Mohiuddin, Amit Arora, Lisa S. Evans, Nathan Bahary, Gamini S. Soori, Janice Eakle, John M. Robertson, Dennis F. Moore Jr, Michael R. Mullane, Benjamin T. Marchello, Patrick J. Ward, Timothy F. Wozniak, Mark S. Roh, Greg Yothers, Norman Wolmark, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; David S. Parda, Norman Wolmark, Allegheny Cancer Center at Allegheny General Hospital; Nathan Bahary, University of Pittsburgh Medical Center and University of Pittsburgh Cancer Institute, Pittsburgh, PA; Robert W. Beart, Colorectal Surgery Institute, Glendale Memorial Hospital, Glendale; Amit Arora, Kaiser Permanente Hayward, Hayward, CA; Nicholas J. Petrelli, Timothy F. Wozniak, Helen F. Graham Cancer Center at Christiana Care Health Service, Newark, DE; Carmen J. Allegra, University of Florida, Gainesville; Janice Eakle, Florida Cancer Specialists, Sarasota; Mark S. Roh, MD Anderson Cancer Center Orlando Health, Orlando, FL; Henry C. Pitot, Mayo Clinic, Rochester, MN; Anthony F. Shields, Karmanos Cancer Institute/Southwest Oncology Group, Detroit; John M. Robertson, Beaumont Hospital System, Royal Oak, MI; Jerome C. Landry, Eastern Cooperative Oncology Group/Emory University, Winship Cancer Institute, Atlanta, GA; David P. Ryan, Massachusetts General Hospital Cancer Center, Boston, MA; Lisa S. Evans, Community Clinical Oncology Program, Southeast CCC Novant Health Derrick L. Davis Forsyth Medical Center, Winston-Salem, NC; Gamini S. Soori, Missouri Valley Cancer Consortium Community Clinical Oncology Program, Omaha, NE; Dennis Moore Jr, Community Clinical Oncology Program, Wichita/St Francis Regional Medical Center/Via Christi Regional Medical Center, Wichita, KS; Michael R. Mullane, Minority-Based Community Clinical Oncology Program John H. Stroger Jr Hospital
| | - Patrick J Ward
- Michael J. O'Connell, Linda H. Colangelo, Robert W. Beart, Nicholas J. Petrelli, Carmen J. Allegra, Saima Sharif, Henry C. Pitot, Anthony F. Shields, David S. Parda, Mohammed Mohiuddin, Amit Arora, Lisa S. Evans, Nathan Bahary, Gamini S. Soori, Janice Eakle, John M. Robertson, Dennis F. Moore Jr, Michael R. Mullane, Benjamin T. Marchello, Patrick J. Ward, Timothy F. Wozniak, Mark S. Roh, Greg Yothers, Norman Wolmark, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; David S. Parda, Norman Wolmark, Allegheny Cancer Center at Allegheny General Hospital; Nathan Bahary, University of Pittsburgh Medical Center and University of Pittsburgh Cancer Institute, Pittsburgh, PA; Robert W. Beart, Colorectal Surgery Institute, Glendale Memorial Hospital, Glendale; Amit Arora, Kaiser Permanente Hayward, Hayward, CA; Nicholas J. Petrelli, Timothy F. Wozniak, Helen F. Graham Cancer Center at Christiana Care Health Service, Newark, DE; Carmen J. Allegra, University of Florida, Gainesville; Janice Eakle, Florida Cancer Specialists, Sarasota; Mark S. Roh, MD Anderson Cancer Center Orlando Health, Orlando, FL; Henry C. Pitot, Mayo Clinic, Rochester, MN; Anthony F. Shields, Karmanos Cancer Institute/Southwest Oncology Group, Detroit; John M. Robertson, Beaumont Hospital System, Royal Oak, MI; Jerome C. Landry, Eastern Cooperative Oncology Group/Emory University, Winship Cancer Institute, Atlanta, GA; David P. Ryan, Massachusetts General Hospital Cancer Center, Boston, MA; Lisa S. Evans, Community Clinical Oncology Program, Southeast CCC Novant Health Derrick L. Davis Forsyth Medical Center, Winston-Salem, NC; Gamini S. Soori, Missouri Valley Cancer Consortium Community Clinical Oncology Program, Omaha, NE; Dennis Moore Jr, Community Clinical Oncology Program, Wichita/St Francis Regional Medical Center/Via Christi Regional Medical Center, Wichita, KS; Michael R. Mullane, Minority-Based Community Clinical Oncology Program John H. Stroger Jr Hospital
| | - Timothy F Wozniak
- Michael J. O'Connell, Linda H. Colangelo, Robert W. Beart, Nicholas J. Petrelli, Carmen J. Allegra, Saima Sharif, Henry C. Pitot, Anthony F. Shields, David S. Parda, Mohammed Mohiuddin, Amit Arora, Lisa S. Evans, Nathan Bahary, Gamini S. Soori, Janice Eakle, John M. Robertson, Dennis F. Moore Jr, Michael R. Mullane, Benjamin T. Marchello, Patrick J. Ward, Timothy F. Wozniak, Mark S. Roh, Greg Yothers, Norman Wolmark, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; David S. Parda, Norman Wolmark, Allegheny Cancer Center at Allegheny General Hospital; Nathan Bahary, University of Pittsburgh Medical Center and University of Pittsburgh Cancer Institute, Pittsburgh, PA; Robert W. Beart, Colorectal Surgery Institute, Glendale Memorial Hospital, Glendale; Amit Arora, Kaiser Permanente Hayward, Hayward, CA; Nicholas J. Petrelli, Timothy F. Wozniak, Helen F. Graham Cancer Center at Christiana Care Health Service, Newark, DE; Carmen J. Allegra, University of Florida, Gainesville; Janice Eakle, Florida Cancer Specialists, Sarasota; Mark S. Roh, MD Anderson Cancer Center Orlando Health, Orlando, FL; Henry C. Pitot, Mayo Clinic, Rochester, MN; Anthony F. Shields, Karmanos Cancer Institute/Southwest Oncology Group, Detroit; John M. Robertson, Beaumont Hospital System, Royal Oak, MI; Jerome C. Landry, Eastern Cooperative Oncology Group/Emory University, Winship Cancer Institute, Atlanta, GA; David P. Ryan, Massachusetts General Hospital Cancer Center, Boston, MA; Lisa S. Evans, Community Clinical Oncology Program, Southeast CCC Novant Health Derrick L. Davis Forsyth Medical Center, Winston-Salem, NC; Gamini S. Soori, Missouri Valley Cancer Consortium Community Clinical Oncology Program, Omaha, NE; Dennis Moore Jr, Community Clinical Oncology Program, Wichita/St Francis Regional Medical Center/Via Christi Regional Medical Center, Wichita, KS; Michael R. Mullane, Minority-Based Community Clinical Oncology Program John H. Stroger Jr Hospital
| | - Mark S Roh
- Michael J. O'Connell, Linda H. Colangelo, Robert W. Beart, Nicholas J. Petrelli, Carmen J. Allegra, Saima Sharif, Henry C. Pitot, Anthony F. Shields, David S. Parda, Mohammed Mohiuddin, Amit Arora, Lisa S. Evans, Nathan Bahary, Gamini S. Soori, Janice Eakle, John M. Robertson, Dennis F. Moore Jr, Michael R. Mullane, Benjamin T. Marchello, Patrick J. Ward, Timothy F. Wozniak, Mark S. Roh, Greg Yothers, Norman Wolmark, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; David S. Parda, Norman Wolmark, Allegheny Cancer Center at Allegheny General Hospital; Nathan Bahary, University of Pittsburgh Medical Center and University of Pittsburgh Cancer Institute, Pittsburgh, PA; Robert W. Beart, Colorectal Surgery Institute, Glendale Memorial Hospital, Glendale; Amit Arora, Kaiser Permanente Hayward, Hayward, CA; Nicholas J. Petrelli, Timothy F. Wozniak, Helen F. Graham Cancer Center at Christiana Care Health Service, Newark, DE; Carmen J. Allegra, University of Florida, Gainesville; Janice Eakle, Florida Cancer Specialists, Sarasota; Mark S. Roh, MD Anderson Cancer Center Orlando Health, Orlando, FL; Henry C. Pitot, Mayo Clinic, Rochester, MN; Anthony F. Shields, Karmanos Cancer Institute/Southwest Oncology Group, Detroit; John M. Robertson, Beaumont Hospital System, Royal Oak, MI; Jerome C. Landry, Eastern Cooperative Oncology Group/Emory University, Winship Cancer Institute, Atlanta, GA; David P. Ryan, Massachusetts General Hospital Cancer Center, Boston, MA; Lisa S. Evans, Community Clinical Oncology Program, Southeast CCC Novant Health Derrick L. Davis Forsyth Medical Center, Winston-Salem, NC; Gamini S. Soori, Missouri Valley Cancer Consortium Community Clinical Oncology Program, Omaha, NE; Dennis Moore Jr, Community Clinical Oncology Program, Wichita/St Francis Regional Medical Center/Via Christi Regional Medical Center, Wichita, KS; Michael R. Mullane, Minority-Based Community Clinical Oncology Program John H. Stroger Jr Hospital
| | - Greg Yothers
- Michael J. O'Connell, Linda H. Colangelo, Robert W. Beart, Nicholas J. Petrelli, Carmen J. Allegra, Saima Sharif, Henry C. Pitot, Anthony F. Shields, David S. Parda, Mohammed Mohiuddin, Amit Arora, Lisa S. Evans, Nathan Bahary, Gamini S. Soori, Janice Eakle, John M. Robertson, Dennis F. Moore Jr, Michael R. Mullane, Benjamin T. Marchello, Patrick J. Ward, Timothy F. Wozniak, Mark S. Roh, Greg Yothers, Norman Wolmark, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; David S. Parda, Norman Wolmark, Allegheny Cancer Center at Allegheny General Hospital; Nathan Bahary, University of Pittsburgh Medical Center and University of Pittsburgh Cancer Institute, Pittsburgh, PA; Robert W. Beart, Colorectal Surgery Institute, Glendale Memorial Hospital, Glendale; Amit Arora, Kaiser Permanente Hayward, Hayward, CA; Nicholas J. Petrelli, Timothy F. Wozniak, Helen F. Graham Cancer Center at Christiana Care Health Service, Newark, DE; Carmen J. Allegra, University of Florida, Gainesville; Janice Eakle, Florida Cancer Specialists, Sarasota; Mark S. Roh, MD Anderson Cancer Center Orlando Health, Orlando, FL; Henry C. Pitot, Mayo Clinic, Rochester, MN; Anthony F. Shields, Karmanos Cancer Institute/Southwest Oncology Group, Detroit; John M. Robertson, Beaumont Hospital System, Royal Oak, MI; Jerome C. Landry, Eastern Cooperative Oncology Group/Emory University, Winship Cancer Institute, Atlanta, GA; David P. Ryan, Massachusetts General Hospital Cancer Center, Boston, MA; Lisa S. Evans, Community Clinical Oncology Program, Southeast CCC Novant Health Derrick L. Davis Forsyth Medical Center, Winston-Salem, NC; Gamini S. Soori, Missouri Valley Cancer Consortium Community Clinical Oncology Program, Omaha, NE; Dennis Moore Jr, Community Clinical Oncology Program, Wichita/St Francis Regional Medical Center/Via Christi Regional Medical Center, Wichita, KS; Michael R. Mullane, Minority-Based Community Clinical Oncology Program John H. Stroger Jr Hospital
| | - Norman Wolmark
- Michael J. O'Connell, Linda H. Colangelo, Robert W. Beart, Nicholas J. Petrelli, Carmen J. Allegra, Saima Sharif, Henry C. Pitot, Anthony F. Shields, David S. Parda, Mohammed Mohiuddin, Amit Arora, Lisa S. Evans, Nathan Bahary, Gamini S. Soori, Janice Eakle, John M. Robertson, Dennis F. Moore Jr, Michael R. Mullane, Benjamin T. Marchello, Patrick J. Ward, Timothy F. Wozniak, Mark S. Roh, Greg Yothers, Norman Wolmark, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; David S. Parda, Norman Wolmark, Allegheny Cancer Center at Allegheny General Hospital; Nathan Bahary, University of Pittsburgh Medical Center and University of Pittsburgh Cancer Institute, Pittsburgh, PA; Robert W. Beart, Colorectal Surgery Institute, Glendale Memorial Hospital, Glendale; Amit Arora, Kaiser Permanente Hayward, Hayward, CA; Nicholas J. Petrelli, Timothy F. Wozniak, Helen F. Graham Cancer Center at Christiana Care Health Service, Newark, DE; Carmen J. Allegra, University of Florida, Gainesville; Janice Eakle, Florida Cancer Specialists, Sarasota; Mark S. Roh, MD Anderson Cancer Center Orlando Health, Orlando, FL; Henry C. Pitot, Mayo Clinic, Rochester, MN; Anthony F. Shields, Karmanos Cancer Institute/Southwest Oncology Group, Detroit; John M. Robertson, Beaumont Hospital System, Royal Oak, MI; Jerome C. Landry, Eastern Cooperative Oncology Group/Emory University, Winship Cancer Institute, Atlanta, GA; David P. Ryan, Massachusetts General Hospital Cancer Center, Boston, MA; Lisa S. Evans, Community Clinical Oncology Program, Southeast CCC Novant Health Derrick L. Davis Forsyth Medical Center, Winston-Salem, NC; Gamini S. Soori, Missouri Valley Cancer Consortium Community Clinical Oncology Program, Omaha, NE; Dennis Moore Jr, Community Clinical Oncology Program, Wichita/St Francis Regional Medical Center/Via Christi Regional Medical Center, Wichita, KS; Michael R. Mullane, Minority-Based Community Clinical Oncology Program John H. Stroger Jr Hospital
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Yoney A, Isikli L. Preoperative chemoradiation in locally advanced rectal cancer: a comparison of bolus 5-fluorouracil/leucovorin and capecitabine. Saudi J Gastroenterol 2014; 20:102-7. [PMID: 24705147 PMCID: PMC3987149 DOI: 10.4103/1319-3767.129474] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
PURPOSE To compare the acute toxicities, pathologic response, surgical margins, downstaging, local control, disease-free survival (DFS), and overall survival (OS) in locally advanced rectal cancer patients with preoperative radiotherapy (RT) with either concurrent bolus 5-fluorouracil (5-FU)/leucovorin (LV) or capecitabine (CA). MATERIALS AND METHODS Sixty patients who presented to our department with a diagnosis of locally advanced rectal cancer were treated with surgery following preoperative RT with either concurrent 5-FU/LV or CA between January 2008 and December 2011 were analyzed. RESULTS Median follow-up period was 38 months (range 3-61). Four patients (6.7%) had grade 3 gastrointestinal (GIS) toxicity during the course of chemoradiotherapy. The pathologic complete response rates were 8% with 5-FU/LV and 8.6% with CA (P = 0.844). Also, 60% of the patients treated with 5-FU/LV and 37.1% with CA had downstaging of the T stage after chemoradiotherapy (P = 0.026). The 5-year local control (P = 0.510), distant control (P = 0.721), DFS (P = 0.08), and OS (P = 0.09) rates were 80%, 80%, 59.4%, and 64.4%, respectively, for patients treated with 5-FU/LV and 85.7%, 82.9%, 74.8%, and 75.1%, respectively, for patients treated with CA. CONCLUSION No significant differences were seen in the local control and distant recurrences and the survival among patients treated with pre-op RT and concurrent 5-FU/LV compared with those treated with pre-op RT and concurrent CA, except toxicities.
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Affiliation(s)
- Adnan Yoney
- Department of Radiation Oncology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey,Address for correspondence: Dr. Adnan Yoney, Department of Radiation Oncology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey. E-mail:
| | - Levent Isikli
- Okmeydani Training and Research Hospital, Istanbul, Turkey
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Berardi R, Maccaroni E, Mantello G, Onofri A, Mandolesi A, Bearzi I, Cascinu S. Locally advanced rectal cancer: new findings in anticancer therapy. COLORECTAL CANCER 2013. [DOI: 10.2217/crc.13.73] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
SUMMARY Rectal cancer accounts for nearly a third of colorectal cancer cases, with a mortality of 4–10 cases per 100,000 per year, thus accounting for 9% of cancer deaths both in males and in females in western countries. Management of locally advanced rectal cancer has undergone and continues to undergo significant progress in the last two decades: in particular, new multimodality strategies have contributed to marked improvements in terms of reduction of both local and distant recurrence rates. This review focuses and summarizes the effectiveness of multimodality approaches in the standard treatment programs for locally advanced rectal cancer and also discusses the ongoing research to improve these regimens.
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Affiliation(s)
- Rossana Berardi
- Medical Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, GM Lancisi, G Salesi, Via Conca 71, 60126 Ancona, Italy
| | - Elena Maccaroni
- Medical Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, GM Lancisi, G Salesi, Via Conca 71, 60126 Ancona, Italy
| | - Giovanna Mantello
- Radiotherapy, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, GM Lancisi, G Salesi, Ancona, Italy
| | - Azzurra Onofri
- Medical Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, GM Lancisi, G Salesi, Via Conca 71, 60126 Ancona, Italy
| | - Alessandra Mandolesi
- Anatomia Patologica, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, GM Lancisi, G Salesi, Ancona, Italy
| | - Italo Bearzi
- Anatomia Patologica, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, GM Lancisi, G Salesi, Ancona, Italy
| | - Stefano Cascinu
- Medical Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, GM Lancisi, G Salesi, Via Conca 71, 60126 Ancona, Italy
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Abstract
Colorectal cancer is the third most common malignancy and cause of cancer-related deaths worldwide. Approximately half of the patients diagnosed with colorectal cancer ultimately die of the condition. Death from colorectal cancer can be prevented by early detection, but unfortunately presentation is often late, with a worse prognosis. Screening by fecal occult blood testing reduces disease-specific mortality, but there is a need for sensitive and specific noninvasive biomarkers to facilitate detecting the disease, staging it, and predicting the best therapeutic options. MicroRNAs (miRNAs) are short noncoding RNA sequences that have a crucial role in the regulation of gene expression. They have significant regulatory functions in basic cellular processes, such as cell differentiation, proliferation, and apoptosis. Evidence suggests that miRNAs may function as both tumor suppressors and oncogenes. The main mechanism for changes in the function of miRNAs in cancer cells is due to aberrant gene expression. Accurate discrimination of miRNA profiles between tumor and normal mucosa in colorectal cancer allows definition of specific expression patterns of miRNAs, giving good potential as diagnostic and therapeutic targets. MiRNAs expressed in colorectal cancers are also abundantly present and stable in stool and plasma samples. Their extraction from these three sources is feasible and reproducible. The ease and reliability of determining miRNA profiles in plasma or stool makes them potential molecular markers for colorectal cancer screening. This review summarizes the role miRNAs have in colorectal cancer, highlighting particularly the potential diagnostic, prognostic, and therapeutic implications in the future treatment of the disease.
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25
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Fernández-Martos C, Nogué M, Cejas P, Moreno-García V, Machancoses AH, Feliu J. The role of capecitabine in locally advanced rectal cancer treatment: an update. Drugs 2012; 72:1057-73. [PMID: 22621694 DOI: 10.2165/11633870-000000000-00000] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Preoperative infusional 5-fluorouracil (5-FU) and concurrent radiation therapy (RT) followed by total mesorectal surgery is the current standard of care for locally advanced rectal cancer (LAR). When compared with postoperative 5-FU-based chemoradiation, this strategy is associated with significantly lower rates of local relapse, lower toxicity and better compliance. Capecitabine is a rationally designed oral prodrug that is converted into 5-FU by intracellular thymidine phosphorylase. Substitution of infusional 5-FU with capecitabine is an attractive option that provides a more convenient administration schedule and, possibly, increased efficacy. Indeed, incorporation of capecitabine in combined modality neoadjuvant therapy for LAR has been under intense investigation during the last 10 years. Phase I and II clinical trials showed that a regimen consisting of capecitabine 825mg/m(2) twice daily for 7 days/week continuous oral administration in combination with RT is an active and well tolerated regimen, thereby being the preferred concurrent regimen. The definitive demonstration that efficacy of capecitabine/RT is similar to 5-FU/RT has been provided by the NSABP-R-04 and the German Margit trials. One approach to improve outcomes in rectal cancer is to deliver a second RT-sensitizing drug with effective systemic activity. Oxaliplatin and irinotecan are therefore good candidates. However, two phase III trials demonstrated that incorporation of oxaliplatin to capecitabine with RT did not improve early outcomes and, by contrast, increased toxicity. Capecitabine has also been combined with irinotecan. This regimen showed encouraging results in phase I and II clinical trials, which led to an ongoing phase III clinical trial. New strategies with induction chemotherapy with or without chemoradiation prior to surgery are currently under investigation. Whether or not capecitabine has a role in this setting is being investigated in ongoing trials. Incorporation of agents directed towards new targets, such as anti-epidermal growth factor receptor (EGFR) antibodies or antiangiogenic agents, in combination preoperative regimens, is being hampered by results of early trials in which efficacy outcomes with cetuximab were poor and an excessive rate of surgical complications with bevacizumab was observed. The lack of improvements in efficacy with the addition of cetuximab or bevacizumab in the adjuvant treatment of colon cancer led to concerns about further development of these agents in rectal cancer. The role of capecitabine in the postoperative adjuvant setting is the aim of the ongoing Dutch SCRIPT trial. The prediction of response associated with capecitabine has been based on expression of thymidylate synthase and dihydropyrimidine dehydrogenase, as well as on gene expression arrays. All these procedures require further validation and should be considered as investigational. In conclusion, capecitabine can safely and effectively replace intravenous continuous infusion of 5-FU in the preoperative chemoradiation setting for rectal cancer management. The addition of other new antineoplastic agents to a fluoropyrimidine-based regimen remains investigational.
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Schroeder C, Gani C, Lamprecht U, von Weyhern CH, Weinmann M, Bamberg M, Berger B. Pathological complete response and sphincter-sparing surgery after neoadjuvant radiochemotherapy with regional hyperthermia for locally advanced rectal cancer compared with radiochemotherapy alone. Int J Hyperthermia 2012; 28:707-14. [DOI: 10.3109/02656736.2012.722263] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
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27
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Chen CF, Huang MY, Huang CJ, Wu CH, Yeh YS, Tsai HL, Ma CJ, Lu CY, Chang SJ, Chen MJ, Wang JY. A observational study of the efficacy and safety of capecitabine versus bolus infusional 5-fluorouracil in pre-operative chemoradiotherapy for locally advanced rectal cancer. Int J Colorectal Dis 2012; 27:727-736. [PMID: 22258885 DOI: 10.1007/s00384-011-1377-3] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/24/2011] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND OBJECTIVES This study is to evaluate the safety and efficacy of preoperative radiotherapy (RT) combined with bolus infusional 5-fluorouracil (5-FU) or oral capecitabine in patients with locally advanced rectal cancer (LARC). MATERIALS AND METHODS Seventy-four patients were retrospectively analyzed. Twenty-seven patients were treated with 5-FU (350 mg/m(2) i.v. bolus) and leucovorin (20 mg/m(2) i.v. bolus) for 5 days/week during week 1 and 5 of RT. Forty-seven patients were treated with capecitabine (850 mg/m(2), twice daily for 5 days/week). Both groups received the same RT course (45-50.4 Gy/25 fractions, 5 days/week, for 5 weeks). Patients underwent surgery in 6 weeks after completion of the chemoradiotherapy. Data of the observational study were collected. RESULTS Grade 3 or 4 toxicities occurred in 40.7% (5-FU) and 19.1% (capecitabine) of the patients (P = 0.044). Six patients in the 5-FU group (22.2%) and six patients in the capecitabine group (14%) achieved complete response. Primary tumor (T) downstaging were achieved in 51.9% (5-FU) and 69.8% (capecitabine) of the patients. The pathological ypT0-2 stage was 40.7% (5-FU) and 67.4% (capecitabine) (P = 0.028). CONCLUSIONS In consideration of the better ypT0-2 downstaging rate, less severe toxicities, and no need for indwelling intravenous device on oral capecitabine regimen, the administration of oral capecitabine with RT may be a more favorable option in the neoadjuvant treatment for LARC.
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Affiliation(s)
- Chin-Fan Chen
- Department of Emergency Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
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Resch G, De Vries A, Öfner D, Eisterer W, Rabl H, Jagoditsch M, Gnant M, Thaler J. Preoperative treatment with capecitabine, bevacizumab and radiotherapy for primary locally advanced rectal cancer – A two stage phase II clinical trial. Radiother Oncol 2012; 102:10-3. [DOI: 10.1016/j.radonc.2011.06.008] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2010] [Revised: 05/18/2011] [Accepted: 06/05/2011] [Indexed: 11/29/2022]
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30
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Grávalos C, García-Alfonso P, Afonso R, Arrazubi V, Arrivi A, Cámara JC, Capdevila J, Gómez-España A, Lacasta A, Manzano JL, Salgado M, Sastre J, Díaz-Rubio E. Recommendations and expert opinion on the treatment of locally advanced rectal cancer in Spain. Clin Transl Oncol 2011; 13:862-8. [PMID: 22126729 DOI: 10.1007/s12094-011-0747-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
Abstract
In Spain 22,000 new cases of colorectal cancer are diagnosed each year, with 13,075 deaths resulting from this disease. Around 70% of colorectal cancers are localised in the colon and 30% in the rectum. A group of Spanish experts established recommendations on what would be the best strategy in the treatment of locally advanced rectal cancer (LARC). Adequate assessment of local tumour extension, including high-resolution magnetic resonance imaging and endorectal ultrasound, is essential for successful treatment. The three cornerstones in the treatment of LARC are surgery, radiotherapy and chemotherapy. Most patients will need a total mesorectal excision (TME). Preoperative chemo-radiotherapy (CRT) is preferred for the majority of patients with T3/T4 disease and/or regional node involvement, and adjuvant chemotherapy is recommended after a patient-sharing decision. Capecitabine, after showing a trend in improved downstaging in neoadjuvant stratum and the convenience of its oral administration, represents an alternative to 5-FU as perioperative treatment of LARC.
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31
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Minsky BD. Progress in the Treatment of Locally Advanced Clinically Resectable Rectal Cancer. Clin Colorectal Cancer 2011; 10:227-37. [DOI: 10.1016/j.clcc.2011.06.007] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2011] [Accepted: 06/21/2011] [Indexed: 12/11/2022]
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Abstract
In the past two decades, substantial progress has been made in the adjuvant management of colorectal cancer. Chemotherapy has improved overall survival in patients with node-positive (N+) disease. In contrast with colon cancer, which has a low incidence of local recurrence, patients with rectal cancer have a higher incidence requiring the addition of pelvic radiation therapy (chemoradiation). Patients with rectal cancer have a number of unique management considerations: for example, the role of short-course radiation, whether postoperative adjuvant chemotherapy is necessary for all patients, and if the type of surgery following chemoradiation should be based on the response rate. More accurate imaging techniques and/or molecular markers may help identify patients with positive pelvic nodes to reduce the chance of overtreatment with preoperative therapy. Will more effective systemic agents both improve the results of radiation as well as modify the need for pelvic radiation? This review will address these and other controversies specific to patients with rectal cancer.
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Affiliation(s)
- Bruce D Minsky
- Department of Radiation and Cellular Oncology, University of Chicago Medical Center, Chicago, IL 60637, USA.
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Park JH, Yoon SM, Yu CS, Kim JH, Kim TW, Kim JC. Randomized phase 3 trial comparing preoperative and postoperative chemoradiotherapy with capecitabine for locally advanced rectal cancer. Cancer 2011; 117:3703-12. [PMID: 21328328 DOI: 10.1002/cncr.25943] [Citation(s) in RCA: 109] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2010] [Revised: 12/14/2010] [Accepted: 12/22/2010] [Indexed: 12/27/2022]
Abstract
BACKGROUND Although many trials have shown the efficacy of preoperative chemoradiotherapy (CRT) or postoperative CRT compared with surgery alone, the optimal sequence of radiotherapy and surgery is unclear. The authors reported the final results of this single institution prospective randomized phase 3 trial comparing preoperative CRT with postoperative CRT using capecitabine in survival, local control, sphincter preservation, and toxicity for the treatment of locally advanced rectal cancer. METHODS Patients with locally advanced rectal cancer (cT3, potentially resectable cT4 or N+) were randomly assigned to receive preoperative or postoperative CRT. CRT consisted of 50 Gy/25 fractions and concurrent capecitabine (1,650 mg/m(2)/day). Total mesorectal excision was performed. RESULTS From March 2004 to April 2006, 240 patients were enrolled. Clinical characteristics were well balanced between both arms, except for more low-lying (<5 cm from anal verge) tumors in the preoperative CRT arm (60% vs 46%, P = .041). After a median follow-up time of 52 months, the 3- and 5-year disease-free survival, overall survival, and cumulative incidence of local recurrence were similar between both arms. However, for the patients with low-lying tumors, the preoperative CRT arm had a higher rate of sphincter preservation (68% vs 42%, P = .008). Acute and late complication rates were similar between both arms. CONCLUSIONS Although significant benefit of preoperative CRT in local control and survival was not demonstrated, the data showed that increased rate of sphincter preservation was possible in low-lying tumors without jeopardizing local control and surgical complication by preoperative CRT.
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Affiliation(s)
- Jin-hong Park
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Minsky BD. Chemoradiation for rectal cancer: rationale, approaches, and controversies. Surg Oncol Clin N Am 2011; 19:803-18. [PMID: 20883955 DOI: 10.1016/j.soc.2010.06.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
The standard adjuvant treatment of cT3 and/or N+ rectal cancer is preoperative chemoradiation. However, there are many controversies regarding this approach. These controversies include the role of short course radiation, whether postoperative adjuvant chemotherapy is necessary for all patients, and if the type of surgery following chemoradiation should be based on the response rate. More accurate imaging techniques and/or molecular markers may help identify patients with positive pelvic nodes to reduce the chance of overtreatment with preoperative therapy. Will more effective systemic agents both improve the results of radiation, as well as modify the need for pelvic radiation? These questions and others remain active areas of clinical investigation.
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Affiliation(s)
- Bruce D Minsky
- Department of Radiation and Cellular Oncology, University of Chicago Medical Center, 5841 South Maryland Avenue, Chicago, IL 60637, USA.
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Long-term results from a randomized phase II trial of neoadjuvant combined-modality therapy for locally advanced rectal cancer. Radiat Oncol 2010; 5:88. [PMID: 20920276 PMCID: PMC2955594 DOI: 10.1186/1748-717x-5-88] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2010] [Accepted: 09/29/2010] [Indexed: 12/14/2022] Open
Abstract
Background This study evaluated the effectiveness and safety of preoperative chemoradiotherapy with capecitabine in patients with locally advanced resectable rectal cancer. This report summarizes the results of the phase II study together with long-term (5-year) follow-up. Methods Between June 2004 and January 2005, 57 patients with operable, clinical stage II-III adenocarcinoma of the rectum entered the study. Radiation dose was 45 Gy delivered as 25 fractions of 1.8 Gy. Concurrent chemotherapy with oral capecitabine 825 mg/m2 twice daily was administered during radiotherapy and at weekends. Surgery was scheduled 6 weeks after the completion of the chemoradiotherapy. Patients received four cycles of postoperative chemotherapy comprising either capecitabine 1250 mg/m2 bid days 1-14 every 3 weeks or bolus i.v. 5-fluorouracil 425 mg/m2/day and leucovorin 20 mg/m2/day days 1-5 every 4 weeks (choice was at the oncologist's discretion). Study endpoints included complete pathological remission, proportion of R0 resections and sphincter-sparing procedures, toxicity, survival parameters and long-term (5-year) rectal and urogenital morbidity assessment. Results One patient died after receiving 27 Gy because of a pulmonary embolism. Fifty-six patients completed radiochemotherapy and had surgery. Median follow-up time was 62 months. No patients were lost to follow-up. R0 resection was achieved in 55 patients. A complete pathological response was observed in 5 patients (9.1%); T-, N- and overall downstaging rates were 40%, 52.9% and 49.1%, respectively. The 5-year overall survival rate, recurrence-free survival, and local control was 61.4% (95% CI: 48.9-73.9%), 52.4% (95% CI: 39.3-65.5%), and 87.4% (95% CI: 75.0-99.8%), respectively. In 5 patients local relapse has occurred; dissemination was observed in 19 patients and secondary malignancies have occurred in 2 patients. The most frequent side-effect of the preoperative combined therapy was dermatitis (grade 3 in 19 patients). The proportion of patients with severe late (SOMA grade 3 and 4) rectal, bladder and sexual toxicity was 40%, 19.2% and 51.7%, respectively. Conclusions This study confirms data from other non-randomised studies that capecitabine-based preoperative chemoradiation is a feasible treatment option for locally advanced rectal cancer, with positive 5-year overall survival, recurrence-free survival, and local control rates.
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Abstract
The standard adjuvant treatment for cT3 and/or N+ rectal cancer is preoperative chemoradiation. However, there are many controversies regarding this approach. These include the role of short course radiation, whether postoperative adjuvant chemotherapy necessary for all patients and whether the type of surgery after chemoradiation should be based on the response rate. More accurate imaging techniques and/or molecular markers may help identify patients with positive pelvic nodes to reduce the chance of overtreatment with preoperative therapy. Will more effective systemic agents both improve the results of radiation as well as modify the need for pelvic radiation? These questions and others remain active areas of clinical investigation.
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Maas M, Nelemans PJ, Valentini V, Das P, Rödel C, Kuo LJ, Calvo FA, García-Aguilar J, Glynne-Jones R, Haustermans K, Mohiuddin M, Pucciarelli S, Small W, Suárez J, Theodoropoulos G, Biondo S, Beets-Tan RGH, Beets GL. Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol 2010; 11:835-44. [PMID: 20692872 DOI: 10.1016/s1470-2045(10)70172-8] [Citation(s) in RCA: 1445] [Impact Index Per Article: 96.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Locally advanced rectal cancer is usually treated with preoperative chemoradiation. After chemoradiation and surgery, 15-27% of the patients have no residual viable tumour at pathological examination, a pathological complete response (pCR). This study established whether patients with pCR have better long-term outcome than do those without pCR. METHODS In PubMed, Medline, and Embase we identified 27 articles, based on 17 different datasets, for long-term outcome of patients with and without pCR. 14 investigators agreed to provide individual patient data. All patients underwent chemoradiation and total mesorectal excision. Primary outcome was 5-year disease-free survival. Kaplan-Meier survival functions were computed and hazard ratios (HRs) calculated, with the Cox proportional hazards model. Subgroup analyses were done to test for effect modification by other predicting factors. Interstudy heterogeneity was assessed for disease-free survival and overall survival with forest plots and the Q test. FINDINGS 484 of 3105 included patients had a pCR. Median follow-up for all patients was 48 months (range 0-277). 5-year crude disease-free survival was 83.3% (95% CI 78.8-87.0) for patients with pCR (61/419 patients had disease recurrence) and 65.6% (63.6-68.0) for those without pCR (747/2263; HR 0.44, 95% CI 0.34-0.57; p<0.0001). The Q test and forest plots did not suggest significant interstudy variation. The adjusted HR for pCR for failure was 0.54 (95% CI 0.40-0.73), indicating that patients with pCR had a significantly increased probability of disease-free survival. The adjusted HR for disease-free survival for administration of adjuvant chemotherapy was 0.91 (95% CI 0.73-1.12). The effect of pCR on disease-free survival was not modified by other prognostic factors. INTERPRETATION Patients with pCR after chemoradiation have better long-term outcome than do those without pCR. pCR might be indicative of a prognostically favourable biological tumour profile with less propensity for local or distant recurrence and improved survival. FUNDING None.
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Affiliation(s)
- Monique Maas
- Department of Surgery, Maastricht University Medical Centre, Maastricht, Netherlands
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Ramani VS, Sun Myint A, Montazeri A, Wong H. Preoperative chemoradiotherapy for rectal cancer: a comparison between intravenous 5-fluorouracil and oral capecitabine. Colorectal Dis 2010; 12 Suppl 2:37-46. [PMID: 20618366 DOI: 10.1111/j.1463-1318.2010.02323.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Capecitabine provides an attractive alternative to intravenous (IV) 5-flourouracil (5-FU) in chemoradiation regimes for rectal cancer by avoiding the need for intravenous access and inpatient stay. We aimed to compare retrospectively the efficacy of concurrent capecitabine with IV 5-FU in preoperative pelvic chemoradiation schedules for rectal cancer in our centre. METHOD Patients treated from January 2005 to June 2007 were included. Information was collected on patient characteristics; treatment details; pathological response to treatment; recurrence and survival. All statistical analyses were performed using SPSS V17. RESULTS All patients had pelvic radiation. Ninety-nine patients were treated with capecitabine and 97 with 5-FU. The two groups were well matched for age, sex and TNM stage. There were significantly more PS (performance status) 0 patients in the capecitabine group (51%vs 30%) (P = 0.001). Of the 99 patients in the capecitabine group, 91 (92%) were able to undergo surgery with 84 (93%) achieving R0 resection. In the 5-FU group, these proportions were 87 (90%) and 70 (80%). The difference in the rate of R0 resection was statistically significant (P = 0.024). The APR rate was 35% in the capecitabine group compared with 47% in the 5-FU group (P = 0.06). There was no significant difference in pathological complete response (pCR) rates between capecitabine (14%) and 5-FU(12%). A higher pCR rate (30%) was observed in patients who underwent a brachytherapy boost (P = 0.051). There were three local recurrences in the whole patient group, (capecitabine 1; 5-FU 2). Thirty-five patients had distant metastases, 14 in the capecitabine and 21 in the 5-FU group. There was no significant difference in the risk of recurrence between the two groups. Six patients in each group had grade 3 toxicity with diarrhoea being more common with capecitabine. CONCLUSIONS Preoperative chemoradiotherapy with capecitabine for rectal cancer is efficacious and comparable to 5-FU (IV). It is more convenient, is well tolerated and avoids the need for inpatient admission.
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Affiliation(s)
- V S Ramani
- Department of Clinical Oncology, Clatterbridge Centre for Oncology, Bebington, Wirral, UK.
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Dihydropyrimidine dehydrogenase polymorphisms and fluoropyrimidine toxicity: ready for routine clinical application within personalized medicine? EPMA J 2010. [PMID: 23199091 PMCID: PMC3405332 DOI: 10.1007/s13167-010-0041-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Fluoropyrimidines, including 5-fluorouracil (5-FU), are widely used in the treatment of solid tumors and remain the backbone of many combination regimens. Despite their clinical benefit, fluoropyrimidines are associated with gastrointestinal and hematologic toxicities, which often lead to treatment discontinuation. 5-FU undergoes complex metabolism, dihydropyrimidine dehydrogenase (DPD) being the rate-limiting enzyme of inactivation of 5-FU and its prodrugs. Several studies have demonstrated significant associations between severe toxicities by fluoropyrimidines and germline polymorphisms of DPD gene. To date, more than 30 SNPs and deletions have been identified within DPD, the majority of these variants having no functional consequences on enzymatic activity. However, the identification of deficient DPD genotypes may help identify poor-metabolizer patients at risk of developing potentially life-threatening toxicities after standard doses of fluoropyrimidines.
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A phase I study of capecitabine, irinotecan, celecoxib, and radiation as neoadjuvant therapy of patients with locally advanced rectal cancer. Am J Clin Oncol 2010; 33:242-5. [PMID: 19806036 DOI: 10.1097/coc.0b013e3181a650fb] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVES We conducted a prospective phase I trial to determine the maximum tolerated dose of capecitabine and irinotecan when used in combination with celecoxib and radiation as preoperative therapy for patients with locally advanced rectal cancer. METHODS Patients with histologic diagnosis of adenocarcinoma of distal rectum, evidence of T3/T4 tumor or nodal involvement by endorectal ultrasound/magnetic resonance imaging, any T status where tumor was close to but not involving the sphincter requiring abdominoperineal resection were evaluated by standard phase I methodology. Starting chemotherapy dosage (dose level: 0) was capecitabine 550 mg/m bid, day 1 to 5 every week through out x-ray therapy, irinotecan 30 mg/ m IV on days 1, 8, 22, 29 (no treatment on day 15 and day 36), and celecoxib 400 mg PO bid from day 1 till the last day of radiation. Radiation dosage of 50.4 Gy in 28 fractions was delivered in 5.6 weeks. If no dose limiting toxicity was observed, dose of capecitabine was escalated by 75 mg/m and irinotecan by 5 mg/m. Celecoxib dosage was fixed. RESULTS Fourteen patients were accrued. Dose limiting toxicity was observed at level 2 and was primarily hematological and gastrointestinal. Two patients at level 2 developed grade-3 diarrhea and thrombocytopenia and 1 patient at level 2 developed grade 3/4 vomiting, diarrhea and dehydration. CONCLUSIONS Recommended dosage for future trials is capecitabine 625 mg/m bid, irinotecan 35 mg/m, and celecoxib 400 mg orally bid in combination with pelvic radiation.
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Wadlow RC, Ryan DP. The role of targeted agents in preoperative chemoradiation for rectal cancer. Cancer 2010; 116:3537-48. [DOI: 10.1002/cncr.25155] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Preoperative Capecitabine and Pelvic Radiation in Locally Advanced Rectal Cancer—Is it Equivalent to 5-FU Infusion Plus Leucovorin and Radiotherapy? Int J Radiat Oncol Biol Phys 2010; 76:1413-9. [DOI: 10.1016/j.ijrobp.2009.03.048] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2009] [Revised: 03/19/2009] [Accepted: 03/23/2009] [Indexed: 12/27/2022]
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Radiothérapie seule ou associée aux traitements médicaux dans les cancers du rectum. ONCOLOGIE 2010. [DOI: 10.1007/s10269-009-1832-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Berardi R, Maccaroni E, Onofri A, Giampieri R, Bittoni A, Pistelli M, Scartozzi M, Pierantoni C, Bianconi M, Cascinu S. Multidisciplinary treatment of locally advanced rectal cancer: a literature review. Part 1. Expert Opin Pharmacother 2009; 10:2245-2258. [PMID: 19640208 DOI: 10.1517/14656560903143776] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
In Western countries, colorectal cancer is the third most common cancer in terms of incidence and mortality. The management of rectal cancer has undergone and continues to undergo significant evolutions. In the last two decades, new multimodality strategies have been developed. Multimodality treatments have improved the prognosis of locally advanced rectal cancer with local recurrences decreasing from 40% to < 10% and overall survival increasing from 50% to 75% in the last 40 years. This review discusses the role of neoadjuvant chemoradiotherapy regimens used in the standard combined modality treatment programs for rectal cancer and focuses on the ongoing research to improve these regimens.
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Affiliation(s)
- Rossana Berardi
- Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I-GM Lancisi-G Salesi di Ancona, Medical Oncology Unit, Ancona, Italy.
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A Liquid Chromatography-Tandem Mass Spectrometry Method for the Determination of 5-Fluorouracil Degradation Rate by Intact Peripheral Blood Mononuclear Cells. Ther Drug Monit 2009; 31:482-8. [DOI: 10.1097/ftd.0b013e3181ae4516] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Das P, Yu TK, Crane CH. In Response to Chien et al. Int J Radiat Oncol Biol Phys 2009. [DOI: 10.1016/j.ijrobp.2008.09.039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Locally Advanced Rectal Cancer: Combined Chemotherapy During Preoperative Radiation Therapy. COLORECTAL CANCER 2009. [DOI: 10.1007/978-1-4020-9545-0_25] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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Bosset JF, Nguyen F, Bosset M, Servagi-Vernat S, Schipman B. Recent advances in the treatment of localized rectal cancer. Curr Oncol Rep 2008; 10:220-4. [PMID: 18765152 DOI: 10.1007/s11912-008-0034-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Randomized clinical trials have recently established preoperative chemoradiotherapy as the new standard treatment for patients with localized cT3-T4 or N+ rectal cancer. Although its inclusion in the modern multidisciplinary management of patients with rectal cancer makes total eradication of pelvic failure a near reality, it does not yet translate into improved survival. As a result, clinical research should be primarily directed against the micrometastatic process, focusing on integrating innovative strategies, such as upfront chemotherapy before chemoradiation, in subgroups of patients recognized to be at high risk.
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Affiliation(s)
- Jean-François Bosset
- Department of Radiation-Oncology, Besançon University Hospital, Boulevard Fleming, F-25030 Besançon Cedex, France.
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Giralt J, Tabernero J, Navalpotro B, Capdevila J, Espin E, Casado E, Mañes A, Landolfi S, Sanchez-Garcia JL, de Torres I, Armengol M. Pre-operative chemoradiotherapy with UFT and Leucovorin in patients with advanced rectal cancer: a phase II study. Radiother Oncol 2008; 89:263-9. [PMID: 18768230 DOI: 10.1016/j.radonc.2008.07.010] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2008] [Revised: 06/30/2008] [Accepted: 07/16/2008] [Indexed: 02/08/2023]
Abstract
PURPOSE The aim this study was to determine the pathologic complete response (pCR) rate defined as tumor regression grade 1 (TRG1) and toxicity profile of the combination of high-dose pre-operative radiotherapy and simultaneous UFT/leucovorin (LV) in patients with locally advanced rectal cancer. MATERIALS/METHODS Eligibility included biopsy proven rectal adenocarcinoma; T3-T4 N0-N2; performance status < 2 (ECOG) and adequate blood, hepatic and renal function. Treatment consisted of radiotherapy 54 Gy at 1.8 Gy/day and UFT 300 mg/m(2)/day and LV 60 mg/day, given simultaneously daily for 6 weeks. Surgery was performed within 4-6 weeks period after chemoradiotherapy. Patients who did not achieve TGR1 were to receive 4 cycles of adjuvant UFT/LV on days 1-28, every 5 weeks. RESULTS Sixty-eight patients were included. All but one received full dose of radiation and 62 had the total planned pre-operative UFT/LV dose. Grade 3 toxicities were diarrhea 7% and proctitis 3%. Complete resection was achieved in 62 patients (91%). Tumor regression grade 1 (TRG1) was seen in 11 patients (16%). Forty-eight patients received adjuvant UFT/LV. Grade 3 toxicity during adjuvant UFT/LV included diarrhea 12%, asthenia 4%, neutropenia 2%, and hand-foot syndrome 2%. The 3-year disease-free survival was 71%. CONCLUSIONS Simultaneous high-dose pre-operative localized radiation therapy concurrent with UFT/LV is feasible and has a low toxicity profile. This schedule is highly effective and merits further investigation.
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Affiliation(s)
- Jordi Giralt
- Department of Radiation Oncology, Vall d'Hebron University Hospital, Barcelona, Spain.
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Phase II study of weekly intravenous oxaliplatin combined with oral daily capecitabine and radiotherapy with biologic correlates in neoadjuvant treatment of rectal adenocarcinoma. Int J Radiat Oncol Biol Phys 2008; 72:650-7. [PMID: 18565686 DOI: 10.1016/j.ijrobp.2008.01.020] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2007] [Revised: 01/05/2008] [Accepted: 01/09/2008] [Indexed: 02/04/2023]
Abstract
PURPOSE To evaluate the efficacy of a combination of capecitabine, oxaliplatin, and radiotherapy (RT) in the neoadjuvant treatment of Stage II and III rectal cancers. METHODS Capecitabine was given at 725 mg/m(2) orally twice daily Monday through Friday concurrently with RT. Oxaliplatin was given intravenously at 50 mg/m(2) once weekly five times starting the first day of RT. The radiation dose was 50.4 Gy in 28 fractions (1.8 Gy/fraction), five fractions weekly. Endorectal tumor biopsies were obtained before treatment and on the third day of treatment to explore the effects of treatment on thymidine phosphorylase, thymidylate synthase, excision repair cross-complementing rodent repair deficiency complementation group 1 (ERCC1), and apoptosis. RESULTS A total of 25 patients were enrolled in this study; 6 patients (24%) had a complete pathologic response. T-downstaging occurred in 52% of patients, and N-downstaging occurred in 53%. Grade 3 diarrhea was the most common Grade 3-4 toxicity, occurring in 20% of patients. Only 2 patients experienced disease recurrence, with a median of 20 months of follow-up. Thymidylate synthase, thymidine phosphorylase, ERCC1, and apoptosis did not vary significantly between the pretreatment and Day 3 tumor biopsies, nor did they predict for T-downstaging or a complete pathologic response. CONCLUSION Capecitabine at 725 mg/m(2) orally twice daily, oxaliplatin 50 mg/m(2)/wk, and RT at 50.4 Gy is an effective neoadjuvant combination for Stage II and III rectal cancer and results in a greater rate of complete pathologic responses than historically shown in fluoropyrimidine plus RT controls.
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