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Saito K, Nakai Y, Takahara N, Ishigaki K, Suzuki Y, Inokuma A, Noguchi K, Kanai S, Sato T, Hakuta R, Saito T, Hamada T, Mizuno S, Kogure H, Ijichi H, Tateishi K, Koike K. A retrospective comparative study of S-IROX and modified FOLFIRINOX for patients with advanced pancreatic cancer refractory to gemcitabine plus nab-paclitaxel. Invest New Drugs 2020; 39:605-613. [PMID: 33094362 DOI: 10.1007/s10637-020-01022-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Accepted: 10/14/2020] [Indexed: 12/26/2022]
Abstract
PURPOSE The aim of this study was to evaluate the efficacy and tolerability of S-IROX and modified FOLFIRINOX (mFFX) after gemcitabine plus nab-paclitaxel for advanced pancreatic cancer (PC) in the real world setting. METHODS Consecutive patients receiving S-IROX or mFFX as a second-line chemotherapy for advanced PC refractory to gemcitabine plus nab-paclitaxel were retrospectively studied. Patients were treated every 2 weeks: S-1 40 mg/m2 was administered orally twice daily on days 1 to 7 in S-IROX and 5-fluorouracil 2400 mg/m2 was intravenously administered for 46 h without bolus infusion in mFFX, in addition to intravenous oxaliplatin 85 mg/m2 and irinotecan 150 mg/m2 on day 1 in both regimens. RESULTS Fifty-four patients with advanced PC who received S-IROX (n = 19) or mFFX (n = 35) were retrospectively studied. The disease control rate and response rate were 73.7% and 10.5% in the S-IROX group and 62.2% and 2.7% in the mFFX group, respectively. The median progression free survival (PFS) was 7.8 and 5.7 months in the S-IROX and mFFX groups (p = 0.24). The median overall survival (OS) was 14.2 and 11.5 months in the S-IROX and mFFX groups (p = 0.34). There were no significant differences in the incidences of grade 3-4 adverse effects. The subgroup analyses suggested S-IROX demonstrated favorable OS in patients with PFS ≥6 months of first-line gemcitabine plus nab-paclitaxel (p for interaction = 0.02). CONCLUSIONS S-IROX and mFFX were similarly tolerable and effective as a second-line chemotherapy in patients with PC refractory to gemcitabine plus nab-paclitaxel.
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Affiliation(s)
- Kei Saito
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Yousuke Nakai
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655, Japan. .,Department of Endoscopy and Endoscopic Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655, Japan.
| | - Naminatsu Takahara
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Kazunaga Ishigaki
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Yukari Suzuki
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Akiyuki Inokuma
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Kensaku Noguchi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Sachiko Kanai
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Tatsuya Sato
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Ryunosuke Hakuta
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655, Japan.,Department of Endoscopy and Endoscopic Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Tomotaka Saito
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Tsuyoshi Hamada
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Suguru Mizuno
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Hirofumi Kogure
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Hideaki Ijichi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Keisuke Tateishi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Kazuhiko Koike
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655, Japan
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Yang SH, Guo JC, Hsu C, Kuo SH, Tien YW, Cheng AL, Yeh KH. Low-dose nab-paclitaxel-based combination chemotherapy in heavily pretreated pancreatic cancer patients. J Formos Med Assoc 2020; 119:97-105. [PMID: 30852003 DOI: 10.1016/j.jfma.2019.01.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2018] [Revised: 11/12/2018] [Accepted: 01/18/2019] [Indexed: 11/20/2022] Open
Abstract
BACKGROUND Heavily pretreated pancreatic cancer patients have a grave prognosis. In this case series study, we evaluated the safety and efficacy of nab-paclitaxel-based chemotherapy for such patients. METHODS The data of pancreatic adenocarcinoma patients (n = 40) treated with nab-paclitaxel after the failure of gemcitabine or fluoropyrimidines at our institution in 2013-2015 were reviewed. RESULTS The median number of prior chemotherapy regimens was two (range, 1-6). Eighteen patients had an Eastern Cooperative Oncology Group performance status of ≥2. The regimens comprised nab-paclitaxel combined with the following drugs: gemcitabine (n = 28), gemcitabine and fluoropyrimidine (n = 3), platinum and fluoropyrimidine (n = 4), fluoropyrimidine (n = 4), and irinotecan and fluoropyrimidine (n = 1). The median dose of nab-paclitaxel was 63 (range, 51-72) mg/m2/dose, with the schedule of D1/15, D1/8, and D1/8/15 followed in 23, 14, and 3 patients, respectively. The median overall survival was 5.1 (95% CI, 4.6-5.7) months. Among 32 evaluable patients, two partial responses and six stable diseases were observed. The median progression-free survival was 2.6 (95% CI, 1.9-3.2) months. Grade 3/4 leucopenia or neutropenia was observed in three and two patients, respectively. Grade 3/4 anemia was observed in four patients. Other significant (grade 3 or more) nonhematological toxicities were not frequent, except for sepsis/infection (n = 7). However, more severe anemia or sepsis/infection was significantly associated with disease control. CONCLUSION In heavily pretreated pancreatic adenocarcinoma patients, low-dose nab-paclitaxel-based chemotherapy was fairly tolerable with modest efficacy.
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Affiliation(s)
- Shih-Hung Yang
- Department of Oncology, National Taiwan University Hospital, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taiwan; Graduate Institutes of Clinical Medicine, National Taiwan University College of Medicine, Taiwan
| | - Jhe-Cyuan Guo
- Department of Oncology, National Taiwan University Hospital, Taiwan; Graduate Institutes of Clinical Medicine, National Taiwan University College of Medicine, Taiwan
| | - Chiun Hsu
- Department of Oncology, National Taiwan University Hospital, Taiwan; Graduate Institutes of Oncology, National Taiwan University College of Medicine, Taiwan
| | - Sung-Hsin Kuo
- Department of Oncology, National Taiwan University Hospital, Taiwan; Graduate Institutes of Oncology, National Taiwan University College of Medicine, Taiwan
| | - Yu-Wen Tien
- Department of Surgery, National Taiwan University Hospital, Taiwan
| | - Ann-Lii Cheng
- Department of Oncology, National Taiwan University Hospital, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taiwan; Graduate Institutes of Oncology, National Taiwan University College of Medicine, Taiwan; National Taiwan University Cancer Center, Taiwan
| | - Kun-Huei Yeh
- Department of Oncology, National Taiwan University Hospital, Taiwan; Graduate Institutes of Clinical Medicine, National Taiwan University College of Medicine, Taiwan; Graduate Institutes of Oncology, National Taiwan University College of Medicine, Taiwan; National Taiwan University Cancer Center, Taiwan.
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Significance and Prevalence of Haziness Surrounding the Hepatic Artery and Celiac Axis on Computed Tomographic Imaging After Pancreaticoduodenectomy. J Comput Assist Tomogr 2018; 42:637-641. [PMID: 29489592 DOI: 10.1097/rct.0000000000000714] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
PURPOSE This study was conducted to assess the prevalence and significance of "haziness" around the hepatic artery and celiac axis in patients after pancreaticoduodenectomy. METHODS This retrospective study was conducted on 116 patients who underwent pancreaticoduodenectomy or a similar procedure and had no clinical evidence of tumor recurrence or malignancy within 2 years from the date of surgery. RESULTS Most images exhibited at least mild to moderate haziness around the hepatic artery and celiac axis. Patients with benign vs malignant results on formal pathology had no significant difference in severity of findings. Haziness remained in the mild to moderate range 2 years after surgery. CONCLUSIONS Mild to moderate soft tissue stranding with increased attenuation around the hepatic artery and celiac axis is a common finding after pancreaticoduodenectomy that may persist for years after surgery. Such haziness alone has low specificity for tumor recurrence and should not be regarded as an indicator of malignancy.
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Chiorean EG, Von Hoff DD, Tabernero J, El-Maraghi R, Ma WW, Reni M, Harris M, Whorf R, Liu H, Li JS, Manax V, Romano A, Lu B, Goldstein D. Second-line therapy after nab-paclitaxel plus gemcitabine or after gemcitabine for patients with metastatic pancreatic cancer. Br J Cancer 2016; 115:188-94. [PMID: 27351217 PMCID: PMC4947701 DOI: 10.1038/bjc.2016.185] [Citation(s) in RCA: 58] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2016] [Revised: 04/29/2016] [Accepted: 05/16/2016] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND This exploratory analysis evaluated second-line (2L) therapy for metastatic pancreatic cancer in a large phase 3 trial (MPACT). METHODS Patients who received first-line (1L) nab-paclitaxel+gemcitabine (nab-P+Gem) or Gem were assessed for survival based on 2L treatment received. Multivariate analyses tested influence of treatment effect and prognostic factors on survival. RESULTS The majority of 2L treatments (267 out of 347, 77%) contained a fluoropyrimidine (5-fluorouracil or capecitabine). Median total survival (1L randomisation to death) for patients who received 2L treatment after 1L nab-P+Gem vs Gem alone was 12.8 vs 9.9 months (P=0.015). Median total survival for patients with a fluoropyrimidine-containing 2L therapy after nab-P+Gem vs Gem was 13.5 vs 9.5 months (P=0.012). Median 2L survival (duration from start of 2L therapy to death) was 5.3 vs 4.5 months for nab-P+Gem vs Gem, respectively (P=0.886). Factors significantly associated with longer post-1L survival by multivariate analyses included 1L nab-P+Gem, receiving 2L treatment, longer 1L progression-free survival, and Karnofsky performance status⩾70 and neutrophil-to-lymphocyte ratio⩽5 at the end of 1L treatment. CONCLUSIONS These findings support the use of 2L therapy for patients with metastatic pancreatic cancer. Fluoropyrimidine-containing treatment after 1L nab-P+Gem is an active regimen with significant clinical effect.
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Affiliation(s)
- E Gabriela Chiorean
- Division Oncology, Department of Medicine, University of Washington, 825 Eastlake Avenue E, G4-833, Seattle, WA 98109-1023, USA
| | - Daniel D Von Hoff
- Translational Genomics Research Institute and HonorHealth, 445 North Fifth Street, Suite 600, Phoenix, AZ 85004, USA
| | - Josep Tabernero
- Vall d'Hebron Institute of Oncology (VHIO), P Vall d'Hebron 119-129, Barcelona 08035, Spain
| | - Robert El-Maraghi
- Royal Victoria Hospital Barrie Canada, 201 Georgian Drive, Barrie, Ontario, Canada L4M 6M2
| | - Wen Wee Ma
- Roswell Park Cancer Institute, 665 Elm Street, Buffalo, NY 14203, USA
| | - Michele Reni
- San Raffaele Scientific Institute, Via Olgetina 60, 20132 Milan, Italy
| | - Marion Harris
- Monash Health, 246 Clayton Road, Melbourne VIC 3168, Australia
| | - Robert Whorf
- Florida Cancer Specialists, 2401 60th Street Ct W, Bradenton, FL 34209-5500, USA
| | - Helen Liu
- Celgene Corporation, 86 Morris Avenue, Summit, NJ 07901, USA
| | | | - Victoria Manax
- Celgene Corporation, 86 Morris Avenue, Summit, NJ 07901, USA
| | - Alfredo Romano
- Celgene Corporation, 86 Morris Avenue, Summit, NJ 07901, USA
| | - Brian Lu
- Celgene Corporation, 86 Morris Avenue, Summit, NJ 07901, USA
| | - David Goldstein
- Department of Medical Oncology, Prince of Wales Hospital, South Sydney Illawarra, Barker Street, Sydney NSW 2031, Australia
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Caparello C, Vivaldi C, Fornaro L, Musettini G, Pasquini G, Catanese S, Masi G, Lencioni M, Falcone A, Vasile E. Second-line therapy for advanced pancreatic cancer: evaluation of prognostic factors and review of current literature. Future Oncol 2016; 12:901-8. [PMID: 26883177 DOI: 10.2217/fon.16.16] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND FOLFIRINOX is a standard first-line treatment for advanced pancreatic cancer (aPC) and no accepted second-line regimen exists. MATERIAL & METHODS We enrolled 71 aPC patients progressed to modified FOLFIRINOX (mFOLFIRINOX) treated with second-line chemotherapy. RESULTS Five partial responses (7.1%) and 19 (27.1%) disease stabilizations were reported. After a median follow-up of 20.1 months, median progression-free survival was 2.5 months (95% CI: 2.1-2.9 months) and median overall survival was 6.2 months (95% CI: 5.3-7.1 months). At multivariate analysis, CA19.9 level ≥ 59 upper normal limit resulted associated with worse survival (hazard ratio: 2.32; 95% CI: 1.12-4.78; p = 0.023). CONCLUSION Salvage chemotherapy could be useful for a subgroup of aPC patients. Prognostic factors might be helpful to identify patients with greater benefit.
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Affiliation(s)
- Chiara Caparello
- Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Pisa, Italy
| | - Caterina Vivaldi
- Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Pisa, Italy
| | - Lorenzo Fornaro
- Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Pisa, Italy
| | - Gianna Musettini
- Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Pisa, Italy
| | - Giulia Pasquini
- Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Pisa, Italy
| | - Silvia Catanese
- Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Pisa, Italy
| | - Gianluca Masi
- Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Pisa, Italy
| | - Monica Lencioni
- Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Pisa, Italy
| | - Alfredo Falcone
- Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Pisa, Italy
| | - Enrico Vasile
- Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Pisa, Italy
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Phase II trial of salvage therapy with trabectedin in metastatic pancreatic adenocarcinoma. Cancer Chemother Pharmacol 2015; 77:477-84. [PMID: 26666646 DOI: 10.1007/s00280-015-2932-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2015] [Accepted: 11/24/2015] [Indexed: 01/04/2023]
Abstract
PURPOSE No standard salvage chemotherapy has been identified for metastatic pancreatic adenocarcinoma (mPA), and there is an urgent need for active agents against this disease. This phase II trial explored the activity of trabectedin in mPA progressing after gemcitabine-based first-line chemotherapy. METHODS Patients with gemcitabine-resistant disease received trabectedin 1.3 mg/m(2) as a 3-h intravenous continuous infusion every 3 weeks until disease progression or unacceptable toxicity or for a maximum of 6 months. The primary endpoint was progression-free survival rate at 6 months (PFS-6). Since trabectedin modulates the production of selected inflammatory mediators, this study also aimed to identify inflammatory biomarkers predictive for response to trabectedin. RESULTS Between February 2011 and February 2012, 25 patients received trabectedin. PFS-6 was 4%, median PFS 1.9 months (range 0.8-7.4), and median overall survival 5.2 months (range 1.1-24.3). Grade >2 toxicity consisted of neutropenia in 44% of patients, febrile neutropenia and thrombocytopenia both in 12%, anemia in 8%, fatigue in 12%, and AST and ALT increase in 8 and 4%, respectively. Trabectedin was shown to modulate the production of inflammatory mediators, and at disease progression, levels of a subgroup of cytokines/chemokines were modified. Furthermore, tissue analysis identified 30 genes associated with better prognosis. CONCLUSIONS Although it has shown some ability to modulate inflammatory process, single-agent trabectedin had no activity as salvage therapy for mPA.
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Nakai Y, Isayama H, Sasaki T, Takahara N, Hamada T, Uchino R, Mizuno S, Miyabayashi K, Yamamoto K, Mohri D, Kogure H, Yamamoto N, Hirano K, Ijichi H, Tateishi K, Tada M, Koike K. A retrospective analysis of early CA19‑9 change in salvage chemotherapy for refractory pancreatic cancer. Cancer Chemother Pharmacol 2014; 72:1291-7. [PMID: 24121456 DOI: 10.1007/s00280-013-2313-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2013] [Accepted: 09/25/2013] [Indexed: 01/12/2023]
Abstract
PURPOSE In salvage chemotherapy for refractory pancreatic cancer, early assessment is important to avoid unnecessary toxicities from ineffective chemotherapy. Early CA19-9 change after the first course as a prognostic factor was evaluated in this setting. METHODS Patients receiving salvage chemotherapy were retrospectively studied. CA19-9 was measured prior to and after the first course. Cox regression analysis was performed for prognostic factors for progression-free survival (PFS) and overall survival (OS), using the landmark method defined as a day of CA19-9 measurement after the first course. RESULTS A total of 239 salvage regimens were given in 167 patients. Median PFS and OS were 2.7 and 6.1 months, respectively. Median pretreatment CA19-9 was 2,362 U/mL, and median CA19-9 change after the first course was 17.8 % increase. CA19-9 change was associated with tumor response, and PFS was 1.7 versus 3.5 months and OS was 3.9 and 8.6 months in patients with ≥50 % versus <50 % increase. In the multivariate analyses, CA19-9 increase ≥50 % was prognostic of both PFS and OS (HR 2.28 and 2.50, p < 0.001, respectively). CONCLUSION CA19-9 change after the first course was prognostic of PFS and OS in refractory pancreatic cancer. Early discontinuation should be considered given the palliative setting.
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Abstract
OBJECTIVES In Belgium, combination chemotherapy of cisplatin and 5-fluorouracil + leucovorin (CFL) according to the modified de Gramont schedule is the treatment of choice in second line for metastatic pancreatic cancer. We retrospectively analyzed survival data in 2 Belgian centers in a nonselected population. METHODS Between January 2004 and October 2011, 48 patients with histologically proven recurrent or unresectable pancreatic adenocarcinoma who had received CFL as second-line treatment were identified. We retrospectively analyzed the following parameters: progression-free survival (PFS1 and PFS2) for each line (after the start of first and second line), overall survival (OS), and growth modulation index. RESULTS The median PFS1 was 5.4 months (95% confidence interval [CI], 4.1-6.6). The median PFS2 was 3.6 months (95% CI, 2-5.2). The median OS was 12 months (95% CI, 9.3-14.7). Twenty-three percent of patients had a growth modulation index >1.33. CONCLUSION We show an OS of 12 months with gemcitabine in first-line and CFL in second-line therapy for pancreatic cancer. Sequential therapy with good OS and good quality of life may be preferred to strong upfront therapy in an incurable disease such as pancreatic cancer.
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Belli C, Cereda S, Reni M. Role of taxanes in pancreatic cancer. World J Gastroenterol 2012; 18:4457-65. [PMID: 22969215 PMCID: PMC3435767 DOI: 10.3748/wjg.v18.i33.4457] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2012] [Revised: 04/09/2012] [Accepted: 04/12/2012] [Indexed: 02/06/2023] Open
Abstract
Pancreatic cancer is one of the most deadly cancers and is characterized by a poor prognosis. Single agent gemcitabine, despite its limited activity and modest impact on disease outcome, is considered as the standard therapy in pancreatic cancer. Most of the combination regimens used in the treatment of this disease, also including the targeted agents, did not improve the outcome of patients. Also, taxanes have been tested as single agent and in combination chemotherapy, both in first line and as salvage chemotherapy, as another possible option for treating pancreatic cancer. The inclusion of taxanes in combination with gemcitabine as upfront therapy obtained promising results. Accordingly, taxanes, and above all, new generation taxanes, appear to be suitable candidates for further testing to assess their role against pancreatic cancer in various clinical settings.
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Taniyama TK, Morizane C, Nakachi K, Nara S, Ueno H, Kondo S, Kosuge T, Shimada K, Esaki M, Ikeda M, Mitsunaga S, Kinoshita T, Konishi M, Takahashi S, Okusaka T. Treatment outcome for systemic chemotherapy for recurrent pancreatic cancer after postoperative adjuvant chemotherapy. Pancreatology 2012; 12:428-33. [PMID: 23127532 DOI: 10.1016/j.pan.2012.07.016] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2012] [Revised: 07/16/2012] [Accepted: 07/17/2012] [Indexed: 02/06/2023]
Abstract
OBJECTIVES A global consensus on how to treat recurrent pancreatic cancer after adjuvant chemotherapy with gemcitabine (ADJ-GEM) does not exist. METHODS We retrospectively reviewed the clinical data of 41 patients with recurrences who were subsequently treated with chemotherapy. RESULTS The patients were divided into two groups according to the time until recurrence after the completion of ADJ-GEM (ADJ-Rec): patients with an ADJ-Rec < 6 months (n = 25) and those with an ADJ-Rec ≥ 6 months (n = 16). The disease control rate, the progression-free survival after treatment for recurrence and the overall survival after recurrence for these two groups were 68 and 94% (P = 0.066), 5.5 and 8.2 months (P = 0.186), and 13.7 and 19.8 months (P = 0.009), respectively. Furthermore, we divided the patients with an ADJ-Rec < 6 months into two groups: patients treated with gemcitabine (n = 6) and those treated with alternative regimens including fluoropyrimidine-containing regimens (n = 19) for recurrent disease. Patients treated with the alternative regimens had a better outcome than those treated with gemcitabine. CONCLUSIONS Fluoropyrimidine-containing regimens may be a reasonable strategy for recurrent disease after ADJ-GEM and an ADJ-Rec < 6 months.
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Affiliation(s)
- Tomoko Katsui Taniyama
- Division of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tsukiji, Chuo-ku, Tokyo, Japan
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Cereda S, Reni M, Rognone A, Fugazza C, Ghidini M, Ceraulo D, Brioschi M, Nicoletti R, Villa E. Salvage therapy with mitomycin and ifosfamide in patients with gemcitabine-resistant metastatic pancreatic cancer: a phase II trial. Chemotherapy 2011; 57:156-61. [PMID: 21454973 DOI: 10.1159/000324865] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2010] [Accepted: 12/13/2010] [Indexed: 12/14/2022]
Abstract
BACKGROUND At the time of upfront treatment failure, over half of the patients with advanced pancreatic cancer are candidates for further treatment. METHODS Patients with metastatic gemcitabine-resistant pancreatic cancer were treated with mitomycin 8 mg/m(2) on day 1, ifosfamide 2,500 mg/m(2) and mesna 3,000 mg/m(2) on days 1-3 every 28 days until progressive disease. A positive responder was defined as a patient who was progression free at 6 months from trial enrollment. According to the Fleming design, a sample size of 34 patients was estimated assuming p0 = 0.05 and p1 = 0.20. RESULTS Between May 2006 and December 2007, 21 patients (median age 56 years; median Karnofsky performance score 80) were enrolled. One patient died before receiving any treatment. Eighteen patients interrupted chemotherapy due to progressive disease (n = 15), toxicity (n = 2) or refusal (n = 1). Grade >2 toxicity consisted of neutropenia in 80% of patients, thrombocytopenia and fatigue in 20% and anemia in 10%. Only 1 patient was progression free at 6 months (5%). One patient had a partial response (5%) and 2 patients had stable disease (10%). Median survival was 3.7 months. CONCLUSION Based on the poor outcome observed and on the high level of grade 3-4 toxicity, the trial was prematurely stopped and the mitomycin and ifosfamide regimen was considered insufficiently active in gemcitabine-pretreated advanced pancreatic cancer.
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Affiliation(s)
- Stefano Cereda
- Department of Oncology, S. Raffaele Scientific Institute, Milan, Italy
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Phase II and coagulation cascade biomarker study of bevacizumab with or without docetaxel in patients with previously treated metastatic pancreatic adenocarcinoma. Am J Clin Oncol 2011; 34:70-5. [PMID: 20458210 DOI: 10.1097/coc.0b013e3181d2734a] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
PURPOSE Treatment options are limited for advanced pancreatic cancer progressive after gemcitabine therapy. The vascular endothelial growth factor pathway is biologically important in pancreatic cancer, and docetaxel has modest antitumor activity. We evaluated the role of the anti-vascular endothelial growth factor antibody bevacizumab as second-line treatment for patients with metastatic pancreatic cancer. DESIGN Patients with metastatic adenocarcinoma of the pancreas who had progressive disease on a gemcitabine-containing regimen were randomized to receive bevacizumab alone or bevacizumab in combination with docetaxel. RESULTS Thirty-two patients were enrolled; 16 to bevacizumab alone (Arm A) and 16 to bevacizumab plus docetaxel (Arm B). Toxicities were greater in Arm B with the most common grade 3/4 nonhematologic toxicities including fatigue, diarrhea, dehydration, and anorexia. No confirmed objective responses were observed. At 4 months, 2 of the 16 patients in Arm A and 3 of the 16 patients in Arm B were free from progression. The study was stopped according to the early stopping rule for futility. Median progression-free survival and overall survival were 43 days and 165 days in Arm A and 48 days and 125 days in Arm B. Elevated d-dimer levels and thrombin-antithrombin complexes were associated with decreased survival and increased toxicity. CONCLUSION Bevacizumab with or without docetaxel does not have antitumor activity in gemcitabine-refractory metastatic pancreatic cancer. Baseline and on-treatment d-dimer and thrombin-antithrombin complex levels are associated with increased toxicity and decreased survival.
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Heye T, Zausig N, Klauss M, Singer R, Werner J, Richter GM, Kauczor HU, Grenacher L. CT diagnosis of recurrence after pancreatic cancer: Is there a pattern? World J Gastroenterol 2011; 17:1126-34. [PMID: 21448416 PMCID: PMC3063904 DOI: 10.3748/wjg.v17.i9.1126] [Citation(s) in RCA: 136] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2010] [Revised: 12/14/2010] [Accepted: 12/21/2010] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate predilection sites of recurrence of pancreatic cancer by computed tomography (CT) in follow-up after surgery.
METHODS: Seventy seven patients with recurrence after pancreatic cancer surgery were retrospectively identified. The operative technique, R-status, T-stage and development of tumor markers were evaluated. Two radiologists analyzed CT scans with consensus readings. Location of local recurrence, lymph node recurrence and organ metastases were noted. Surgery and progression of findings on follow-up CT were considered as reference standard.
RESULTS: The mean follow-up interval was 3.9 ± 1.8 mo, with a mean relapse-free interval of 12.9 ± 10.4 mo. The predominant site of recurrence was local (65%), followed by lymph node (17%), liver metastasis (11%) and peritoneal carcinosis (7%). Local recurrence emerged at the superior mesenteric artery (n = 28), the hepatic artery (n = 8), in an area defined by the surrounding vessels: celiac trunk, portal vein, inferior vena cava (n = 22), and in a space limited by the mesenteric artery, portal vein and inferior vena cava (n = 17). Lymph node recurrence occurred in the mesenteric root and left lateral to the aorta. Recurrence was confirmed by surgery (n = 22) and follow-up CT (n = 55). Tumor markers [carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA)] increased in accordance with signs of recurrence in most cases (86% CA19-9; 79.2% CEA).
CONCLUSION: Specific changes of local and lymph node recurrence can be found in the course of the cardinal peripancreatic vessels. The superior mesenteric artery is the leading structure for recurrence.
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O'Reilly EM, Niedzwiecki D, Hall M, Hollis D, Bekaii-Saab T, Pluard T, Douglas K, Abou-Alfa GK, Kindler HL, Schilsky RL, Goldberg RM. A Cancer and Leukemia Group B phase II study of sunitinib malate in patients with previously treated metastatic pancreatic adenocarcinoma (CALGB 80603). Oncologist 2010; 15:1310-9. [PMID: 21148613 PMCID: PMC3227926 DOI: 10.1634/theoncologist.2010-0152] [Citation(s) in RCA: 53] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2010] [Accepted: 10/08/2010] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND The Cancer and Leukemia Group B (CALGB) conducted a phase II study evaluating sunitinib in patients with progressive metastatic pancreas adenocarcinoma following prior gemcitabine-based therapy (trial CALGB 80603; ClinicalTrials.gov identifier, NCT00397787). The primary endpoint was to determine the disease control rate (DCR) as measured by the Response Evaluation Criteria in Solid Tumors (complete response, partial response [PR], and stable disease) at 6 weeks. PATIENTS AND METHODS Patients aged ≥18 years with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2 and with progressive pancreas adenocarcinoma following treatment with gemcitabine were eligible. Sunitinib was dosed at 50 mg orally days 1-28, every 42 days (1 cycle). The statistical plan called for a three-stage design. A DCR ≥15% was considered worthy of further study. RESULTS In total, 77 patients were enrolled. Forty-two (54.6%) enrollees were male. The median age was 65 years. The ECOG performance status score distribution was: 0, 39%; 1, 50%; 2, 11%. The DCR was 21.6%; one patient (1.4%) had a PR and 15 patients (20.3%) had stable disease as their best response. The progression-free survival time was 1.31 months (95% confidence interval [CI] 1.25-1.38 months) and overall survival time was 3.68 months (95% CI, 3.06-4.24 months). CONCLUSIONS The study met its primary endpoint; however sunitinib had minimal activity and moderate toxicity in a population of gemcitabine-refractory pancreas adenocarcinoma patients. For future studies, limiting enrollment to patients with an ECOG performance status score of 0-1 is recommended.
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Affiliation(s)
- Eileen M O'Reilly
- Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
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Haas M, Laubender RP, Stieber P, Holdenrieder S, Bruns CJ, Wilkowski R, Mansmann U, Heinemann V, Boeck S. Prognostic relevance of CA 19-9, CEA, CRP, and LDH kinetics in patients treated with palliative second-line therapy for advanced pancreatic cancer. Tumour Biol 2010; 31:351-7. [PMID: 20480409 DOI: 10.1007/s13277-010-0044-6] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2010] [Accepted: 02/26/2010] [Indexed: 12/18/2022] Open
Abstract
The objective of this study was to define prognostic serum biomarkers that could serve as surrogate survival endpoints during second-line treatment for advanced pancreatic cancer. This retrospective single-center study included patients treated with second-line therapy for advanced exocrine pancreatic cancer. A pretreatment value and at least one serial measurement during the first two cycles of second-line chemotherapy for CA 19-9, CEA, CRP, and LDH had to be available in order to evaluate the prognostic role of kinetics on overall survival. A cutoff of a >20% increase from baseline during treatment was defined in order to form groups with suspected different outcomes. The effect of serial biomarker changes on survival was modeled by Cox proportional hazards regression in univariate and multivariate analyses. Overall, 70 patients treated with second-line therapy for advanced disease were included; 94% had distant metastases at treatment initiation. Median time to progression was 2.7 months and median survival 5.4 months. Univariate analysis found that an increase of >20% during treatment was significantly associated with a worse overall survival for CA 19-9 (HR 2.00, p = 0.018), CEA (HR 2.38, p = 0.004), and CRP (HR 3.06, p < 0.001). These associations remained significant within multivariate analysis for CEA (HR 2.86, p = 0.001) and CRP (HR 3.20, p = 0.001). Serum biomarker kinetics might serve as useful prognostic tools during second-line chemotherapy in advanced pancreatic cancer.
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Affiliation(s)
- Michael Haas
- Department of Internal Medicine III, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, 81377 Munich, Germany
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