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Babaier A, Ghatage P. Mucinous Cancer of the Ovary: Overview and Current Status. Diagnostics (Basel) 2020; 10:E52. [PMID: 31963927 PMCID: PMC7168201 DOI: 10.3390/diagnostics10010052] [Citation(s) in RCA: 63] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2019] [Revised: 01/13/2020] [Accepted: 01/15/2020] [Indexed: 02/06/2023] Open
Abstract
Mucinous ovarian cancer (MOC) is a rare subtype of epithelial ovarian carcinoma (EOC). Whereas all EOC subtypes are addressed in the same way, MOC is a distinct entity. Appreciating the pathological features and genomic profile of MOC may result in the improvement in management and, hence, the prognosis. Distinguishing primary MOC from metastatic mucinous carcinoma can be challenging but is essential. Early-stage MOC carries an excellent prognosis, with advanced disease having a poor outcome. Surgical management plays an essential role in the early stage and in metastatic disease. Chemotherapy is usually administered for stage II MOC and beyond. The standard gynecology protocol is frequently used, but gastrointestinal regimens have also been administered. As MOC is associated with multiple molecular alterations, targeted therapy could be the answer to treat this disease.
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Affiliation(s)
- Abdulaziz Babaier
- Department of Gynecologic Oncology, King Fahad Specialist Hospital, Dammam 32253, Saudi Arabia
| | - Prafull Ghatage
- Department of Gynecologic Oncology, Tom Baker Cancer Centre, Calgary, AB T2N4N2, Canada;
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2
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Thorat SG, Chikhale RV, Tajne MR. Development and Validation of HPLC and HPTLC Methods for Therapeutic Drug Monitoring of Capecitabine in Colorectal Cancer Patients. J Chromatogr Sci 2020; 57:892-900. [PMID: 31609432 DOI: 10.1093/chromsci/bmz067] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2018] [Revised: 06/15/2019] [Indexed: 12/18/2022]
Abstract
Capecitabine is a prodrug of 5-fluorouracil, employed as a monotherapy or combination chemotherapy agent for treatment of colorectal cancer. Combination therapy of capecitabine consists of oxaliplatin, and hence, it becomes essential to determine that co-administration does not affect its metabolism. High-performance liquid chromatography and high-performance thin-layer chromatography methods were developed and validated to determine the plasma concentration of capecitabine. In this study, blood samples from 12 patients with colorectal cancer were collected and analyzed by both methods with a reference internal standard. Two groups consisting of six patients each were formed: the first group was treated with capecitabine monotherapy, the second group with capecitabine + oxaliplatin combination therapy. The results of analysis from both the methods indicated that there is no significant drug-drug interaction. The co-administration of oxaliplatin did not affect the metabolism of capecitabine. Both assay methods were compared for their sensitivity, robustness and specificity. It was found that both the assay methods were suitable for therapeutic drug monitoring of capecitabine.
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Affiliation(s)
- Sonali G Thorat
- Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Mahatma Jyotiba Fuley Shaikshanik Parisar, Amravati Road, Nagpur-440033, Maharashtra, India
| | - Rupesh V Chikhale
- Division of Pharmacy and Optometry, University of Manchester, Manchester M13 9PL, UK
| | - Madhukar R Tajne
- Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Mahatma Jyotiba Fuley Shaikshanik Parisar, Amravati Road, Nagpur-440033, Maharashtra, India
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3
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Lau G, Alwan L, Chi M, Lentz M, Hone K, Segal E. Expanding pharmacy practice through the use of pharmacy technicians as process navigators to facilitate patient access of oral anticancer agents. J Am Pharm Assoc (2003) 2019; 59:586-592. [DOI: 10.1016/j.japh.2019.03.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2018] [Revised: 02/28/2019] [Accepted: 03/01/2019] [Indexed: 11/28/2022]
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Gore M, Hackshaw A, Brady WE, Penson RT, Zaino R, McCluggage WG, Ganesan R, Wilkinson N, Perren T, Montes A, Summers J, Lord R, Dark G, Rustin G, Mackean M, Reed N, Kehoe S, Frumovitz M, Christensen H, Feeney A, Ledermann J, Gershenson DM. An international, phase III randomized trial in patients with mucinous epithelial ovarian cancer (mEOC/GOG 0241) with long-term follow-up: and experience of conducting a clinical trial in a rare gynecological tumor. Gynecol Oncol 2019; 153:541-548. [PMID: 31005287 PMCID: PMC6559214 DOI: 10.1016/j.ygyno.2019.03.256] [Citation(s) in RCA: 55] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2019] [Accepted: 03/26/2019] [Indexed: 12/18/2022]
Abstract
OBJECTIVES We evaluated four different treatment regimens for advanced-stage mucinous epithelial ovarian cancer. METHODS We conducted a multicenter randomized factorial trial (UK and US). Patients were diagnosed with primary mEOC: FIGO stage II-IV or recurrence after stage I disease. Treatment arms were paclitaxel-carboplatin, oxaliplatin-capecitabine, paclitaxel-carboplatin-bevacizumab, or oxaliplatin-capecitabine-bevacizumab. Chemotherapy was given 3-weekly for 6 cycles, and bevacizumab (3-weekly) was continued as maintenance (for 12 cycles). Endpoints included overall-survival (OS), progression-free survival (PFS), toxicity and quality of life (QoL). RESULTS The trial stopped after 50 patients were recruited due to slow accrual. Median follow-up was 59 months. OS hazard ratios (HR) for the two main comparisons were: 0.78 (p = 0.48) for Oxal-Cape vs. Pac-Carbo (each with/without bevacizumab), and 1.04 (p = 0.92) for bevacizumab vs. no bevacizumab. Corresponding PFS HRs were: 0.84 and 0.80. Retrospective central pathology review revealed only 45% (18/40) cases with available material had confirmed primary mEOC. Among these, OS HR for Oxal-Cape vs. Pac-Carbo was 0.36 (p = 0.14); PFS HR = 0.62 (p = 0.40). Grade 3-4 toxicity was seen in 61% Pac-Carbo, 61% Oxal-Cape, 54% Pac-Carbo-Bev, and 85% Oxal-Cape-Bev. QoL was similar between the four arms. CONCLUSION mEOC/GOG0241 represents an example of a randomized rare tumor trial. Logistical challenges led to early termination, including difficulties in local histopathological diagnosis and accessing drugs outside their labelled indication. There was misalignment between central funders who support clinical trials in rare cancers and the deprioritisation of such work by those managing and funding research at a local level. Rare cancer trials should include centralised pathology review before treatment. Clinical trial registry number: ISRCTN83438782.
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MESH Headings
- Adult
- Aged
- Aged, 80 and over
- Antineoplastic Combined Chemotherapy Protocols/adverse effects
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use
- Bevacizumab/administration & dosage
- Capecitabine/administration & dosage
- Carboplatin/administration & dosage
- Carcinoma, Ovarian Epithelial/drug therapy
- Carcinoma, Ovarian Epithelial/secondary
- Female
- Follow-Up Studies
- Humans
- Internationality
- Middle Aged
- Neoplasm Recurrence, Local/drug therapy
- Neoplasms, Cystic, Mucinous, and Serous/drug therapy
- Neoplasms, Cystic, Mucinous, and Serous/secondary
- Ovarian Neoplasms/drug therapy
- Ovarian Neoplasms/pathology
- Oxaliplatin/administration & dosage
- Paclitaxel/administration & dosage
- Progression-Free Survival
- Quality of Life
- Response Evaluation Criteria in Solid Tumors
- Survival Rate
- Young Adult
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Affiliation(s)
- Martin Gore
- Royal Marsden NHS Foundation Trust, London, UK
| | - Allan Hackshaw
- Cancer Research UK & UCL Cancer Trials Centre, London, UK.
| | | | | | - Richard Zaino
- Penn State Health Milton S. Hershey Medical Centre, PA, USA
| | | | | | - Nafisa Wilkinson
- University College London Hospitals NHS Foundation Trust, London, UK
| | | | - Ana Montes
- Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Jeffrey Summers
- Maidstone and Tunbridge Wells NHS Foundation Trust, Kent, UK
| | - Rosemary Lord
- Clatterbridge Cancer Centre NHS Foundation Trust, Liverpool, UK
| | - Graham Dark
- Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | | | | | | | - Sean Kehoe
- Institute of Cancer and Genomics, University of Birmingham, Birmingham, UK
| | | | | | - Amanda Feeney
- Cancer Research UK & UCL Cancer Trials Centre, London, UK
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Safety and Efficacy of Low-Dose Single-Agent Capecitabine in Inoperable Gallbladder Cancer with Jaundice Post-Single-System Single-Catheter External Biliary Drainage: a Pilot Study from a Highly Endemic Area. Indian J Surg Oncol 2018; 9:530-537. [PMID: 30538384 DOI: 10.1007/s13193-018-0798-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2017] [Accepted: 07/13/2018] [Indexed: 12/28/2022] Open
Abstract
Gallbladder cancer (CaGB) in the subcontinent belongs to low socioeconomic status, and at the time of diagnosis, a large number is unresectable or inoperable so the palliative treatment remains the only option. In the present study, attempt was made to see the effect and safety profile of single-agent oral capecitabine in inoperable CaGB in presence of low levels of jaundice post-single-catheter transhepatic external biliary drainage. In N = 35 of inoperable jaundiced CaGB, post-biliary drainage capecitabine in low dose was started when their total bilirubin levels fell to 10 mg% or below. Post-external drainage decreased bilirubin level to < 10 mg/dl within 1-4 weeks, mean 2.37 ± 0.80 weeks. Survival was 1-6 months, mean 3.26 ± 1.46 months. Catheter patency time was 1.92 ± 0.64 months (range 0-3 months). Young age, male sex, level of jaundice at presentation, and duration of decrease in jaundice after drainage were significantly associated with progressive disease course. Poor survival was significantly associated with progressive disease course, young age, and level of jaundice at admission. To the best of our knowledge, this is the first study to establish that single-agent capecitabine can be safely given in CaGB in presence of jaundice.
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Hata T, Takahashi H, Sakai D, Haraguchi N, Nishimura J, Kudo T, Chu M, Takemasa I, Taroh S, Mizushima T, Doki Y, Mori M. Neoadjuvant CapeOx therapy followed by sphincter-preserving surgery for lower rectal cancer. Surg Today 2017; 47:1372-1377. [PMID: 28474202 DOI: 10.1007/s00595-017-1527-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2016] [Accepted: 03/13/2017] [Indexed: 12/18/2022]
Abstract
PURPOSE This retrospective study investigates the safety of neoadjuvant chemotherapy with oxaliplatin capecitabine (CapeOx), followed by laparoscopic surgery, for lower rectal cancer, and its efficacy in preserving the sphincter. METHODS Ten patients with diagnosed lower rectal cancer received three or four cycles of neoadjuvant CapeOx chemotherapy, prior to undergoing low anterior resection or intersphincteric resection, with total mesorectal excision. The primary outcomes were R0 resection and the rate of sphincter preservation. RESULTS Nine patients completed CapeOx as scheduled and a partial response was achieved in four; thus, the overall response rate was 40% (n = 4/10). After surgical intervention, 80% of tumors displayed downstaging. Postoperative anastomosis leakage developed in one patient. The distance from the anal verge to the tumor increased by 60% (median 1.5 cm) after CapeOx treatment. The anal sphincter was preserved in all patients and all pathological distal and radial margins were negative (R0 resections). A pathological complete response was achieved in one patient. CONCLUSIONS Neoadjuvant CapeOx chemotherapy is a promising approach, because it extended the distance from the anus to the tumor. Subsequent laparoscopic intervention for advanced lower rectal cancer could allow for safe preservation of the sphincter.
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Affiliation(s)
- Taishi Hata
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 E2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
| | - Hidekazu Takahashi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 E2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Daisuke Sakai
- Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Suita, Japan
| | - Naotsugu Haraguchi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 E2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Junichi Nishimura
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 E2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Toshihiro Kudo
- Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Suita, Japan
| | - Matsuda Chu
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 E2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Ichiro Takemasa
- Department of Surgery, Surgical Oncology and Science, Graduate School of Medicine, Sapporo Medical University, Sapporo, Japan
| | - Satoh Taroh
- Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Suita, Japan
| | - Tsunekazu Mizushima
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 E2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 E2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Masaki Mori
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 E2 Yamadaoka, Suita, Osaka, 565-0871, Japan
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Fishbein JN, Nisotel LE, MacDonald JJ, Amoyal Pensak N, Jacobs JM, Flanagan C, Jethwani K, Greer JA. Mobile Application to Promote Adherence to Oral Chemotherapy and Symptom Management: A Protocol for Design and Development. JMIR Res Protoc 2017; 6:e62. [PMID: 28428158 PMCID: PMC5418526 DOI: 10.2196/resprot.6198] [Citation(s) in RCA: 70] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2016] [Revised: 12/09/2016] [Accepted: 02/14/2017] [Indexed: 01/04/2023] Open
Abstract
Background Oral chemotherapy is increasingly used in place of traditional intravenous chemotherapy to treat patients with cancer. While oral chemotherapy includes benefits such as ease of administration, convenience, and minimization of invasive infusions, patients receive less oversight, support, and symptom monitoring from clinicians. Additionally, adherence is a well-documented challenge for patients with cancer prescribed oral chemotherapy regimens. With the ever-growing presence of smartphones and potential for efficacious behavioral intervention technology, we created a mobile health intervention for medication and symptom management. Objective The objective of this study was to develop and evaluate the usability and acceptability of a smartphone app to support adherence to oral chemotherapy and symptom management in patients with cancer. Methods We used a 5-step development model to create a comprehensive mobile app with theoretically informed content. The research and technical development team worked together to develop and iteratively test the app. In addition to the research team, key stakeholders including patients and family members, oncology clinicians, health care representatives, and practice administrators contributed to the content refinement of the intervention. Patient and family members also participated in alpha and beta testing of the final prototype to assess usability and acceptability before we began the randomized controlled trial. Results We incorporated app components based on the stakeholder feedback we received in focus groups and alpha and beta testing. App components included medication reminders, self-reporting of medication adherence and symptoms, an education library including nutritional information, Fitbit integration, social networking resources, and individually tailored symptom management feedback. We are conducting a randomized controlled trial to determine the effectiveness of the app in improving adherence to oral chemotherapy, quality of life, and burden of symptoms and side effects. At every stage in this trial, we are engaging stakeholders to solicit feedback on our progress and next steps. Conclusions To our knowledge, we are the first to describe the development of an app designed for people taking oral chemotherapy. The app addresses many concerns with oral chemotherapy, such as medication adherence and symptom management. Soliciting feedback from stakeholders with broad perspectives and expertise ensured that the app was acceptable and potentially beneficial for patients, caregivers, and clinicians. In our development process, we instantiated 7 of the 8 best practices proposed in a recent review of mobile health app development. Our process demonstrated the importance of effective communication between research groups and technical teams, as well as meticulous planning of technical specifications before development begins. Future efforts should consider incorporating other proven strategies in software, such as gamification, to bolster the impact of mobile health apps. Forthcoming results from our randomized controlled trial will provide key data on the effectiveness of this app in improving medication adherence and symptom management. Trial Registration ClinicalTrials.gov NCT02157519; https://clinicaltrials.gov/ct2/show/NCT02157519 (Archived by WebCite at http://www.webcitation.org/6prj3xfKA)
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Affiliation(s)
- Joel Nathan Fishbein
- Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, United States
| | - Lauren Ellen Nisotel
- Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, United States
| | - James John MacDonald
- Department of Psychology, University of California, Los Angeles, Los Angeles, CA, United States
| | - Nicole Amoyal Pensak
- Anschutz Medical Campus, Department of Medicine, University of Colorado Denver, Denver, CO, United States
| | - Jamie Michele Jacobs
- Center for Psychiatric Oncology and Behavioral Sciences, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.,Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
| | - Clare Flanagan
- Partners Connected Health, Partners HealthCare, Boston, MA, United States.,Department of Global Health and Population, Harvard TH Chan School of Public Health, Boston, MA, United States
| | - Kamal Jethwani
- Partners Connected Health, Partners HealthCare, Boston, MA, United States.,Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
| | - Joseph Andrew Greer
- Center for Psychiatric Oncology and Behavioral Sciences, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.,Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
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Zulkapli R, Abdul Razak F, Zain RB. Vitamin E (α-Tocopherol) Exhibits Antitumour Activity on Oral Squamous Carcinoma Cells ORL-48. Integr Cancer Ther 2016; 16:414-425. [PMID: 28818030 PMCID: PMC5759939 DOI: 10.1177/1534735416675950] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Cancers involving the oral cavity, head, and neck regions are often treated with cisplatin. In cancer therapy, the main target is to eliminate unwanted cancerous cells. However, reports on the nonselective nature of this drug have raised few concerns. Incorrect nutritional habits and lifestyle practices have been directly linked to cancer incidence. Nutrients with antioxidant activity inhibit cancer cells development, destroying them through oxidative stress and apoptosis. α-tocopherol, the potent antioxidant form of vitamin E is a known scavenger of free radicals. In vitro study exhibited effective antitumor activity of α-tocopherol on ORL-48 at 2.5 ± 0.42 µg/mL. Cisplatin exhibited stronger activity at 1.0 ± 0.15 µg/mL, but unlike α-tocopherol it exhibited cytotoxicity on normal human epidermal keratinocytes at very low concentration (<0.1 µg/mL). Despite the lower potency of α-tocopherol, signs of apoptosis such as the shrinkage of cells and appearance of apoptotic bodies were observed much earlier than cisplatin in time lapse microscopy. No apoptotic vesicles were formed with cisplatin, instead an increased population of cells in the holoclone form which may suggest different induction mechanisms between both agents. High accumulation of cells in the G0/G1 phase were observed through TUNEL and annexin V-biotin assays, while the exhibition of ultrastructural changes of the cellular structures verified the apoptotic mode of cell death by both agents. Both cisplatin and α-tocopherol displayed cell cycle arrest at the Sub G0 phase. α-tocopherol thus, showed potential as an antitumour agent for the treatment of oral cancer and merits further research.
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Affiliation(s)
- Rahayu Zulkapli
- 1 Department of Oral and Craniofacial Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.,2 Centre of Preclinical Science Study, Faculty of Dentistry, Universiti Teknologi Mara, Selangor, Malaysia
| | - Fathilah Abdul Razak
- 1 Department of Oral and Craniofacial Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia
| | - Rosnah Binti Zain
- 3 Department of Oro-maxillofacial Surgical & Medical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.,4 Oral Cancer Research and Coordinating Centre, University of Malaya, Kuala Lumpur, Malaysia
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Mamo A, Easaw J, Ibnshamsah F, Baig A, Rho YS, Kavan T, Batist G, Kavan P. Retrospective analysis of the effect of CAPOX and mFOLFOX6 dose intensity on survival in colorectal patients in the adjuvant setting. ACTA ACUST UNITED AC 2016; 23:171-7. [PMID: 27330345 DOI: 10.3747/co.23.3059] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND Despite lack of a true comparative study, the folfox (5-fluorouracil-leucovorin-oxaliplatin) and capox (capecitabine-oxaliplatin) regimens are believed to be similar in their efficacy and tolerability in the treatment of stage iii colorectal cancer. However, that belief has been disputed, because real-life data suggest that the capox regimen is more toxic, leading to more frequent reductions in the delivered dose intensity-thus raising questions about the effect of dose intensity on clinical outcomes. METHODS A retrospective data review for two Canadian institutions, the Segal Cancer Centre and the Tom Baker Cancer Centre, considered patients diagnosed with stage iii colorectal cancer during 2006-2013. Primary endpoints were dose intensity and toxicity, with a secondary endpoint of disease-free survival. RESULTS The study enrolled 180 eligible patients (80 at the Segal Cancer Centre, 100 at the Tom Baker Cancer Centre). Of those 180 patients, 75 received capox, and 105 received mfolfox6. In the capox group, a significant dose reduction was identified for capecitabine compared with 5-fluorouracil in mfolfox6 group (p = 0.0014). Similarly, a significant dose reduction was observed for oxaliplatin in mfolfox6 compared with oxaliplatin in capox (p = 0.0001). Compared with the patients receiving capox, those receiving mfolfox6 were twice as likely to experience a treatment delay of more than 1 cycle-length (p = 0.03855). Toxicity was more frequent in patients receiving mfolfox6 (nausea: 30% vs. 18%; diarrhea: 47% vs. 24%; peripheral sensory neuropathy: 32% vs. 3%). At a median follow-up of 40 months, preliminary data showed no difference in disease-free survival (p = 0.598). Pooled data from both institutions were also separately analyzed, and no significant differences were found. CONCLUSIONS Our results support the use of capox despite a lack of head-to-head randomized trial data.
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Affiliation(s)
- A Mamo
- Department of Oncology, McGill University, and the Segal Cancer Centre, Sir Mortimer B. Davis Jewish General Hospital, Montreal, QC
| | - J Easaw
- Tom Baker Cancer Centre, Calgary, AB
| | | | - A Baig
- Department of Oncology, McGill University, and the Segal Cancer Centre, Sir Mortimer B. Davis Jewish General Hospital, Montreal, QC
| | - Y S Rho
- Department of Oncology, McGill University, and the Segal Cancer Centre, Sir Mortimer B. Davis Jewish General Hospital, Montreal, QC
| | - T Kavan
- Department of Oncology, McGill University, and the Segal Cancer Centre, Sir Mortimer B. Davis Jewish General Hospital, Montreal, QC
| | - G Batist
- Department of Oncology, McGill University, and the Segal Cancer Centre, Sir Mortimer B. Davis Jewish General Hospital, Montreal, QC
| | - P Kavan
- Department of Oncology, McGill University, and the Segal Cancer Centre, Sir Mortimer B. Davis Jewish General Hospital, Montreal, QC
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10
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Patel JN, Fong MK. Personalizing fluoropyrimidine administration in colorectal cancer patients. EXPERT REVIEW OF PRECISION MEDICINE AND DRUG DEVELOPMENT 2016. [DOI: 10.1080/23808993.2016.1176860] [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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11
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Coli S, Pigazzani F, Gaibazzi N. Midventricular Takotsubo cardiomyopathy after oxaliplatin infusion: an unreported side effect. J Cardiovasc Med (Hagerstown) 2016; 16:646-9. [PMID: 25333375 DOI: 10.2459/jcm.0000000000000204] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
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12
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Munemoto Y, Kanda M, Ishibashi K, Hata T, Kobayashi M, Hasegawa J, Fukunaga M, Takagane A, Otsuji T, Miyake Y, Nagase M, Sakamoto J, Matsuoka M, Oba K, Mishima H. Capecitabine and oxaliplatin combined with bevacizumab are feasible for treating selected Japanese patients at least 75 years of age with metastatic colorectal cancer. BMC Cancer 2015; 15:786. [PMID: 26497654 PMCID: PMC4619505 DOI: 10.1186/s12885-015-1712-0] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2015] [Accepted: 10/08/2015] [Indexed: 02/07/2023] Open
Abstract
Background Although number of elderly patients with metastatic colorectal cancer (mCRC) is rapidly increasing, this population is often underrepresented in clinical trials. Recently, a phase II trial demonstrated that capecitabine and oxaliplatin (XELOX) combined with bevacizumab XELOX plus bevacizumab was effective and well tolerated by elderly patients with mCRC who reside in Western countries. The aim of this study was to evaluate the safety and efficacy of XELOX plus bevacizumab for Japanese patients aged ≥75 years with mCRC. Methods This prospective, open-label phase II trial recruited patients aged ≥75 years with previously untreated mCRC between March 2010 and January 2012. Treatment consisted of 7.5 mg/kg of intravenous bevacizumab and 130 mg/m2 of oxaliplatin on day 1 of each cycle combined with 2000 mg/m2 of oral capecitabine per day on days 1–14 of each cycle. Treatment was repeated every 3 weeks until disease progression or termination of the study. The primary endpoint was progression-free survival; the secondary endpoints were toxicity, overall response rate, time-to-treatment failure, and overall survival. Results Thirty-six patients (male 58 %; median age 78 years; colon cancer 67 %) met all eligibility criteria and received at least one course of the planned treatment. The median time-to-treatment failure was 7.0 months. Twelve patients (33.3 %) experienced adverse effects (AEs) ≥ grade 3 and frequent AEs ≥ grade 3, including neutropenia (22.2 %) and neuropathy (13.9 %). Hypertension was the most frequent AE ≥ grade 3 associated with bevacizumab (11.1 %). Low baseline creatinine clearance associated significantly with the incidence of AEs ≥ grade 3. Response and disease control rates were 55.6 and 91.7 %, respectively. Median progression-free and overall survival times were 11.7 months (95 % confidence interval, 8.0–13.4 months) and 22.9 months, respectively. Conclusion XELOX combined with bevacizumab was well tolerated by selected Japanese patients aged ≥75 years with mCRC patients, and controlled clinical trials are now required to determine the survival benefit. Electronic supplementary material The online version of this article (doi:10.1186/s12885-015-1712-0) contains supplementary material, which is available to authorized users.
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Affiliation(s)
| | - Mitsuro Kanda
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
| | - Keiichiro Ishibashi
- Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Kawagoe, Japan.
| | - Taishi Hata
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
| | - Michiya Kobayashi
- Department of Human Health and Medical Sciences, Kochi Medical School, Kohasu, Japan.
| | | | - Mutsumi Fukunaga
- Department of Surgery, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Japan.
| | - Akinori Takagane
- Surgical Division, Hakodate Goryoukaku Hospital, Hakodate, Japan.
| | - Toshio Otsuji
- Department of Internal Medicine, Dongo Hospital, Yamatotakada, Nara, Japan.
| | - Yasuhiro Miyake
- Department of Surgery, Minoh City Hospital Gastrointestinal Research Center, Minoh, Osaka, Japan.
| | - Michitaka Nagase
- Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Japan.
| | | | | | - Koji Oba
- Department of Biostatistics, School of Public Health, Tokyo University Graduate School of Medicine, Tokyo, Japan. .,Interfaculty Initiative in Information Studies, Tokyo University, Tokyo, Japan.
| | - Hideyuki Mishima
- Unit of Cancer Center, Aichi Medical University, Nagakute, Japan.
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13
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Spoelstra SL, Given BA, Given CW, Grant M, Sikorskii A, You M, Decker V. Issues related to overadherence to oral chemotherapy or targeted agents. Clin J Oncol Nurs 2015; 17:604-9. [PMID: 24113679 DOI: 10.1188/13.cjon.17-06ap] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Use of oral chemotherapy or targeted agents is shifting how cancer treatment is administered, moving it from supervised office visits to self-administration at home. This study examines issues related to overadherence to oral agents that were noted during a trial conducted by the authors comparing an automated voice system to strategies to reduce symptom severity and improve adherence. Overadherence to oral agents may be a significant clinical problem, occurring more often in patients with complex dosing regimens, and may lead to increased symptom severity from side effects of treatment. Avoiding overadherence may be important for the reduction or prevention of symptoms and potentially life-threatening toxicity. Nurses need to discuss with their patients the importance of the timing of the administration of their oral oncolytic regimen, as well as to provide prompts to assist in self-administration as prescribed so that overadherence can be avoided.
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Iqbal S, Lenz HJ. Capecitabine: the new generation of fluoropyrimidines in colorectal cancer. Expert Rev Anticancer Ther 2014; 4:947-55. [PMID: 15606325 DOI: 10.1586/14737140.4.6.947] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Colorectal cancer is the second leading cause of cancer death in the USA and fluoropyrimidines have been the mainstay of treatment for over 40 years. Currently, capecitabine is the only orally available fluoropyrimidine approved for treatment in the USA. As a single agent it has demonstrated activity and equivalence to 5-fluorouracil (5-FU) intravenous administration via the Mayo Clinic regimen, in both the metastatic and adjuvant settings. Ongoing clinical trials are evaluating the efficacy of capecitabine in combination with oxaliplatin and irinotecan as more convenient substitutes for infusional 5-FU in the 5-FU/leucovorin/oxaliplatin and 5-FU/irinotecan regimens.
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Affiliation(s)
- Syma Iqbal
- University of Southern California, Kenneth Norris Comprehensive Cancer Center, Division of Medical Oncology, 1441 Eastlake Avenue, Suite 3457, Los Angeles, CA 90033, USA.
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Carrato A, Gallego-Plazas J, Guillén-Ponce C. Capecitabine plus oxaliplatin for the treatment of colorectal cancer. Expert Rev Anticancer Ther 2014; 8:161-74. [DOI: 10.1586/14737140.8.2.161] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
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16
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Bordonaro S, Romano F, Lanteri E, Cappuccio F, Indorato R, Butera A, D’Angelo A, Ferraù F, Tralongo P. Effect of a structured, active, home-based cancer-treatment program for the management of patients on oral chemotherapy. Patient Prefer Adherence 2014; 8:917-23. [PMID: 25028540 PMCID: PMC4077854 DOI: 10.2147/ppa.s62666] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
INTRODUCTION The advent of oral chemotherapy agents has had a strong impact on several aspects of the management of cancer patients, including survival rates, health-care expenditure, and health-related quality of life. However, access to care and adherence to oral chemotherapy are central to optimal outcomes. PATIENTS AND METHODS In this multicenter observational study, we assessed the effect of the "Active Home Care" initiative - a structured, active, home-based cancer-treatment program - on quality of life, health-care utilization, and patient adherence and satisfaction using self-administered questionnaires. Sixty-two patients treated with oral chemotherapy (capecitabine, vinorelbine, imatinib, sunitinib, sorafenib, temozolomide, ibandronate) were enrolled in the program. Weekly home visits were scheduled, each one with a trained nurse who delivered the home-based chemotherapy and reviewed patients' compliance and treatment toxicity. An oncologist evaluated patients and modified the dosage of oral chemotherapy based on toxicity reported during the previous cycle at bi-weekly visits. RESULTS A total of 460 home visits were performed between April 2012 and February 2013. The Active Home Care initiative was associated with significant improvements in physical functioning and symptoms, and reductions in the access to cancer facilities. Satisfaction with oral chemotherapy and care received was high. All patients reported having taken their medications according to their prescription, and no patient reported difficulties in managing the oral chemotherapy regimen. CONCLUSION The Active Home Care program was associated with improvements in the quality of life of patients and caregivers, better adherence to treatment, and the effective management of therapy and cancer-related symptoms. Home-based cancer treatment may also optimize the utilization of health-care resources.
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Affiliation(s)
- S Bordonaro
- Medical Oncology Unit, Umberto I Hospital, Rete Assistenza Oncologica, Siracusa, Italy
| | - F Romano
- Medical Oncology Unit, Umberto I Hospital, Rete Assistenza Oncologica, Siracusa, Italy
| | - E Lanteri
- Medical Oncology Unit, Umberto I Hospital, Rete Assistenza Oncologica, Siracusa, Italy
| | - F Cappuccio
- Medical Oncology Unit, Umberto I Hospital, Rete Assistenza Oncologica, Siracusa, Italy
| | - R Indorato
- Medical Oncology Unit, S Giovanni di Dio Hospital, Agrigento, Italy
| | - A Butera
- Medical Oncology Unit, S Giovanni di Dio Hospital, Agrigento, Italy
| | - A D’Angelo
- Medical Oncology Unit, S Vincenzo Hospital, Taormina, Italy
| | - F Ferraù
- Medical Oncology Unit, S Vincenzo Hospital, Taormina, Italy
| | - P Tralongo
- Medical Oncology Unit, Umberto I Hospital, Rete Assistenza Oncologica, Siracusa, Italy
- Correspondence: Paolo Tralongo, Medical Oncology Unit, Umberto I Hospital, RAO, Siracusa, Italy, Tel +39 9 3172 4542, Email
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Abstract
PURPOSE Important developments in chemotherapy for advanced colorectal cancer over the past 15 years are reviewed, with an emphasis on the most recently published data from clinical trials of newer multidrug regimens, administration techniques, and dosing schedules. SUMMARY Eight agents are approved by the Food and Drug Administration (FDA) for use in treating patients with advanced colorectal cancer. Fluorouracil and leucovorin still constitute the foundation of most chemotherapy regimens for this population; combination fluorouracil-leucovorin therapy plus either irinotecan (the FOLFIRI regimen) or oxaliplatin (the FOLFOX regimen) are two firmly established first-line treatments shown to produce similar outcomes. In Phase III trials conducted over the past six to seven years, regimens of capecitabine plus oxaliplatin (CapeOx) were demonstrated to have clinical effectiveness comparable to that of FOLFOX therapy. Response rates of 35-55% and median overall survival of ≥20 months have been documented with some of the newer regimens. Research to define the optimal role of the three monoclonal antibody agents approved by FDA for use in managing advanced colorectal cancer is ongoing; bevacizumab has been shown to confer significant survival benefits when added to certain chemotherapy regimens, and other monoclonal antibodies (cetuximab and panitumumab) also appear to offer significant benefits in select patients as first- or second-line therapies. CONCLUSION Over the past 15 years, a shift toward multiagent treatment strategies including a variety of chemotherapy agents and monoclonal antibodies has yielded improved rates of response and prolonged survival among patients with advanced colorectal cancer. The CapeOx, FOLFOX, and FOLFIRI regimens are currently among the most widely used first-line treatments.
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Affiliation(s)
- Robert J Cersosimo
- School of Pharmacy, Bouvé College of Health Sciences, Northeastern University, Boston, MA 02115, USA.
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de Gramont A, Chibaudel B, Bonnetain F, Dumont S, Larsen AK, André T. Clinical Reasons for Initiation of Adjuvant Phase III Trials on Colon Cancer. CURRENT COLORECTAL CANCER REPORTS 2013. [DOI: 10.1007/s11888-013-0176-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
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Krikorian SA, Shamim K. Adherence Issues for Oral Antineoplastics. Am J Lifestyle Med 2013. [DOI: 10.1177/1559827612466996] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Nonadherence to antineoplastics is a growing concern because of the increasing number of novel oral targeted anticancer therapies. Many of these agents are administered on a chronic continuous schedule for an indefinite period of time where adherence is crucial to achieve optimal disease control and prolong survival. Many factors are known to contribute to medication nonadherence. Prevention, early detection, and management of adverse drug reactions associated with oral targeted therapies require close vigilance. Knowing how to prevent and manage adverse drug reactions will help clinicians develop strategies to promote patient adherence to oral anticancer treatment regimens. Optimal adherence requires a dynamic patient-provider alliance through education, communication, ongoing monitoring, and follow-up.
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Affiliation(s)
- Susan A. Krikorian
- Massachusetts College of Pharmacy and Health Sciences, Boston, Massachusetts (SAK, KS)
- Mount Auburn Hospital, Cambridge, Massachusetts (SAK)
| | - Kanza Shamim
- Massachusetts College of Pharmacy and Health Sciences, Boston, Massachusetts (SAK, KS)
- Mount Auburn Hospital, Cambridge, Massachusetts (SAK)
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Biweekly XELOX (capecitabine and oxaliplatin) as first-line treatment in elderly patients with metastatic colorectal cancer. J Geriatr Oncol 2013; 4:114-21. [PMID: 24071536 DOI: 10.1016/j.jgo.2013.01.001] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2012] [Revised: 09/28/2012] [Accepted: 01/17/2013] [Indexed: 12/24/2022]
Abstract
OBJECTIVE The combination of oxaliplatin and oral capecitabine (XELOX) has shown to be an active regimen in metastatic colorectal cancer (MCRC). However, the experience with XELOX in elderly patients is limited. This study aimed to evaluate the efficacy and safety of XELOX as first-line treatment in elderly patients with MCRC. PATIENTS AND METHODS Patients aged ≥70years with previously untreated MCRC received oxaliplatin 85mg/m(2) on day 1, every 2weeks plus capecitabine 1000mg/m(2) (or capecitabine 750mg/m(2) if creatinine clearance was 30-50mL/min) twice daily on days 1-7, every 2weeks. Treatment was continued until progression, intolerable toxicity, or for a maximum of 12cycles. RESULTS Thirty-five patients were enrolled. Median age was 78years (range, 70-83). Patients received a median of 11cycles of treatment. The objective response rate (ORR) was 49% and the tumor control rate was 86%. Median time to progression and overall survival were 8.6 (95% CI: 5.5-11.7) and 15.5 (95% CI: 9.6-21.3) months, respectively. Toxicities were generally mild to moderate. Major grade 1-2 toxicities were asthenia (40%), nausea (43%), and diarrhea (40%). No grade 4 toxicity was detected and grade 3 toxicities were reported in 17% of patients. There was no treatment-related death. CONCLUSION Our findings show that the biweekly XELOX regimen represents an effective and tolerable first-line treatment option for elderly patients with MCRC.
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21
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Zhang C, Wang J, Gu H, Zhu D, Li Y, Zhu P, Wang Y, Wang J. Capecitabine plus oxaliplatin compared with 5-fluorouracil plus oxaliplatin in metastatic colorectal cancer: Meta-analysis of randomized controlled trials. Oncol Lett 2012; 3:831-838. [PMID: 22741002 DOI: 10.3892/ol.2012.567] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2011] [Accepted: 01/04/2012] [Indexed: 12/27/2022] Open
Abstract
The aim of this study was to evaluate the curative effects and safety of capecitabine plus oxaliplatin compared with 5-fluorouracil (5-FU) plus oxaliplatin in patients with metastatic colorectal cancer (MCRC). We searched the Cochrane Central register of Controlled Trials (CENTRAL), PubMed, Ovid, ScienceDirect, EBSCO, EMBASE and conference proceedings for eligible trials. A meta-analysis was performed using Review Manager 5.0. A total of 3,603 cancer patients from 7 trials were analyzed, and the baseline patient characteristics were comparable in all studies. Curative effect outcomes including complete response (CR) (OR=0.78; 95% CI 0.47-1.31; p=0.35), partial response (PR) (OR=0.81; 95% CI 0.65-1.00; p=0.05) and the overall response rate (ORR) (OR=0.85; 95% CI 0.71-1.02; p=0.08) showed similar curative effects between the capecitabine plus oxaliplatin group and the 5-FU plus oxaliplatin group. Moreover, the median overall survival (OS) and progression-free survival (PFS) had no statistically significant differences. Regarding safety, hand-foot syndrome was more frequently observed in the capecitabine plus oxaliplatin group (OR=2.71; 95% CI 2.04-3.61; p<0.00001), while stomatitis and neutropenia were reversed. Other toxic effects had no statistically significant differences between the two groups. Our results showed that capecitabine plus oxaliplatin had similar curative effects to 5-FU plus oxaliplatin, however, it was safer in patients with MCRC.
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Affiliation(s)
- Chengyao Zhang
- Department of General Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China
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22
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Treatment dilemmas in patients with synchronous colorectal liver metastases. Recent Results Cancer Res 2012; 196:37-49. [PMID: 23129365 DOI: 10.1007/978-3-642-31629-6_3] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Approximately 20 % of patients with colorectal cancer have synchronous liver metastases at the time of diagnosis. In some instances it is difficult to determine the best treatment strategy in these patients. For example, should the primary tumor be removed in those patients with unresectable liver metastases and who do not have any symptoms of the primary tumor? Or which operation should be performed first in patients with rectal cancer and synchronous resectable liver metastases? Unfortunately, there are no clear answers to these questions from prospective randomized trials. In the present article retrospective studies are analyzed in order to define the best possible treatment strategy for patients with synchronous colorectal liver metastases.
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Wahba HA, El-Hadaad HA, Abd-Ellatif EA. Neoadjuvant concurrent chemoradiotherapy with capecitabine and oxaliplatin in patients with locally advanced esophegeal cancer. Med Oncol 2011; 29:1693-8. [PMID: 21706368 DOI: 10.1007/s12032-011-0001-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2011] [Accepted: 05/27/2011] [Indexed: 12/15/2022]
Abstract
Evaluation of the feasibility and efficacy of neoadjuvant concurrent chemoradiotherapy (CRT) with capecitabine and oxaliplatin in patients with locally advanced esophageal cancer. Forty-two patients were eligible for the study. The chemotherapy during CRT consisted of two cycles of intravenous oxaliplatin of 120 mg/m(2) on day 1 and oral capecitabine 825 mg/m(2) twice daily on days 1-14 at 3-week intervals. The radiotherapy (1.8 Gy/fraction/day to a total dose of 45 Gy) was delivered to the primary tumor site and regional lymph node. All patients completed the planned treatment. Overall clinical response rate was 54.8% with complete response in 16.7% while pathological response rate was 38%. Anemia was the commonest hematologic toxicity (52.3%) with grade 3 in 4.7%, and esophagitis was the commonest non-hematologic toxicity 59.5% with grade 3 and 4 in 9.5%. No treatment-related death was observed. After a median follow-up duration of 19 months, the 2-year survival rate was 42%, median survival time was 20 months (95%CI: 13.802-26.198), while 2-year progression-free survival (PFS) rate was 32.5% with median PFS time of 15 months (95%CI: 10.042-19.958). Neoadjuvant concurrent CRT with capecitabine and oxaliplatin was found to be well tolerated and effective in patients with locally advanced esophageal cancer; however, these results should be further evaluated in a phase III study.
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Affiliation(s)
- Hanan Ahmed Wahba
- Department of Clinical Oncology and Nuclear Medicine, Mansoura University, Mansoura, Egypt
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24
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Spoelstra SL, Given CW. Assessment and Measurement of Adherence to Oral Antineoplastic Agents. Semin Oncol Nurs 2011; 27:116-32. [DOI: 10.1016/j.soncn.2011.02.004] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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Wong NS, Fernando NH, Bendell JC, Morse MA, Blobe GC, Honeycutt W, Pang H, Hurwitz HI. A phase II study of oxaliplatin, dose-intense capecitabine, and high-dose bevacizumab in the treatment of metastatic colorectal cancer. Clin Colorectal Cancer 2011; 10:210-6. [PMID: 21855046 DOI: 10.1016/j.clcc.2011.03.018] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2010] [Revised: 12/02/2010] [Accepted: 12/06/2010] [Indexed: 02/04/2023]
Abstract
BACKGROUND This study was designed to determine the efficacy and tolerability of a novel 2-week regimen of capecitabine, oxaliplatin (OHP), and bevacizumab in patients with chemo-naive advanced colorectal cancer. PATIENTS AND METHODS Nineteen patients with previously untreated advanced colorectal cancer received capecitabine at 1000 mg/m(2) twice a day on days 1-5 and days 8-12 of a 14-day cycle, and OHP at 85 mg/m(2) and bevacizumab at 10 mg/kg every 2 weeks. Because of unacceptable toxicities, the capecitabine dose was reduced to 850 mg/m(2). Thirty-one additional patients were treated at the lower capecitabine dose. Treatment continued until disease progression, persistent intolerable toxicity, or physician and/or patient discretion. RESULTS Overall, toxicities were better managed and tolerated at the 850 mg/-m(2) capecitabine dose. The most common treatment-related grade ≥ 3 toxicities were diarrhea and sensory neuropathy. In the first 19 subjects, the response rate was 63% (95% confidence interval [CI], 38%-84%) and 5 patients had stable disease; median progression-free survival (PFS) was 10.1 months (95% CI, 5.7-19.5 months). In the subsequent 31 patients, the response was 42% (95% CI, 25%-61%); 11 patients had stable disease and median PFS was 10.4 months (95% CI, 6.9-15.4); median overall survival was 24.8 months (95% CI, 12.9-39.7). CONCLUSIONS This novel regimen of capecitabine at 850 mg/m(2) twice a day on days 1-5 and days 8-12 and OHP at 85 mg/m(2)and bevacizumab at 10 mg/kg every 14 days is clinically active in advanced colorectal cancer. The toxicity profile of this regimen is consistent with the standard every-3-week dosing schedule.
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Lindsay CR, Cassidy J. XELOX in colorectal cancer: a convenient option for the future? Expert Rev Gastroenterol Hepatol 2011; 5:9-19. [PMID: 21309667 DOI: 10.1586/egh.10.90] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
XELOX is a 3-weekly chemotherapy combination of oral capecitabine and intravenous oxaliplatin. The central hypothesis that led to its development was that it would provide a convenient and cost-effective alternative to intravenous fluorouracil-based chemotherapy doublets, without compromising on anti-tumor efficacy. Recently its role in colorectal cancer has become more established in both the metastatic and adjuvant setting. Ongoing investigation of XELOX continues in a number of directions: its combination with novel biological agents, its efficacy and safety in the elderly, and the development of biomarkers that can predict its anti-tumor effect. This article provides a comprehensive and up-to-date synopsis of all pertinent clinical studies detailing this regimen and its promise for the future.
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Affiliation(s)
- Colin R Lindsay
- Beatson West of Scotland Cancer Centre, 1053 Great Western Road, Glasgow G12 0YN, UK.
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27
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A Phase Ib pharmacokinetic study of the anti-angiogenic agent CKD-732 used in combination with capecitabine and oxaliplatin (XELOX) in metastatic colorectal cancer patients who progressed on irinotecan-based chemotherapy. Invest New Drugs 2010; 30:672-80. [PMID: 21188464 DOI: 10.1007/s10637-010-9625-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2010] [Accepted: 12/16/2010] [Indexed: 02/05/2023]
Abstract
BACKGROUND We conducted a Phase I clinical trial to evaluate the safety, tolerability, and pharmacokinetics (PK) of CKD-732 [6-O-(4-dimethylaminoethoxy) cinnamoyl fumagillol hemioxalate] in combination with capecitabine and oxaliplatin (XELOX) in nine metastatic colorectal cancer patients who had progressed on irinotecan-based chemotherapy. METHODS Using a dose-escalation schedule, CKD-732 doses of 2, 5, or 10 mg/m(2)/d were administered twice weekly for 2 weeks, followed by a 1-week rest. Oxaliplatin (130 mg/m(2)) was administered on day 1, and capecitabine (1,000 mg/m(2) twice a day) was orally administered for 14 days of a 3-week cycle. RESULTS In the group given the 10 mg/m(2)/d dose, two patients experienced dose limiting toxicities (one had grade 3 nausea, insomnia, and fatigue; the other had grade 3 insomnia). The maximum tolerated dose was 10 mg/m(2)/d, and the clinically recommended dose was 5 mg/m(2)/d for CKD-732 in combination with XELOX. Frequently encountered non-hematological grade 3/4 adverse events included insomnia (22.2%), fatigue (11.1%), sensory neuropathy (11.1%), hyperbilirubinemia (11.1%), and dyspnea (11.1%). The area under the concentration-time curve and maximum concentration of CKD-732 increased in a dose-dependent manner. There were no notable effects of CKD-732 on the PK of capecitabine and oxaliplatin-derived platinum. CONCLUSION The Phase II recommended dose of CKD-732 was determined to be 5 mg/m(2)/d, and this dose was safely combined with a conventional dose of capecitabine and oxaliplatin in this patient population. Further studies on the effects of CKD-732 in combination with XELOX and other chemotherapies using a larger study population are warranted.
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Silvestris N, Maiello E, De Vita F, Cinieri S, Santini D, Russo A, Tommasi S, Azzariti A, Numico G, Pisconti S, Petriella D, Lorusso V, Millaku A, Colucci G. Update on capecitabine alone and in combination regimens in colorectal cancer patients. Cancer Treat Rev 2010; 36 Suppl 3:S46-55. [DOI: 10.1016/s0305-7372(10)70020-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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Malik I, Bernal P, Byrd J. A phase I study of docetaxel, oxaliplatin, & capecitabine (DOC) as first-line therapy of patients with locally advanced or metastatic adenocarcinoma of stomach and GE junction. Cancer Invest 2010; 28:833-8. [PMID: 20839949 DOI: 10.3109/07357901003630942] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
PURPOSE We conducted a phase I trial of chemotherapy in patients with advanced gastro-esophageal cancer. METHODS Eligible patients had chemotherapy doses increased until dose limiting toxicity (DLT) was observed. RESULTS Fourteen patients were accrued. No DLT was observed in first three patients at level 1. DLT was observed in two out of five patients at level 2. Six additional patients were treated at level 1. CONCLUSIONS Recommended doses for future trials are: docetaxel 30 mg/m(2) and oxaliplatin 50 mg/m(2) on days 1 and 8 and capecitabine 675 mg/m(2) PO, bid, on days 1-14 on a three weekly basis.
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Affiliation(s)
- Imtiaz Malik
- Loma Linda Oncology Medical Group Inc, Claremont, CA 91711, USA.
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Teng CJ, Hsieh YY, Chen KW, Chao TC, Tzeng CH, Wang WS. Sudden-onset pancytopenia with intracranial hemorrhage after oxaliplatin treatment: a case report and literature review. Jpn J Clin Oncol 2010; 41:125-9. [PMID: 20826449 DOI: 10.1093/jjco/hyq162] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
Oxaliplatin is a third-generation platinum compound and has been widely employed in the treatment of colorectal cancer. Despite its good efficacy, it is reported to induce immune-mediated cytopenia. We report the case of a 78-year-old male patient who experienced acute pancytopenia along with coagulopathy and intracranial hemorrhage after his 17th course of oxaliplatin. This condition appeared immediately after completion of oxaliplatin infusion, and was persistent despite aggressive transfusion and treatment with granulocyte colony-stimulating factor. The patient died 72 h after the administration of oxaliplatin. The only preceding symptom was chills 30 min after initiation of oxaliplatin, although steroid was given as premedication. We review the literature describing oxaliplatin-induced cytopenia, and discuss the manifestation, immune mechanism and treatment of this condition. We conclude that any symptoms that occur during infusion of oxaliplatin should not be overlooked but should be taken seriously as they may represent 'a little spark that kindles a great fire', and that steroids may provide an effective treatment for oxaliplatin-induced cytopenia. However, a major complication in our patient may still happen. Further studies for the mechanism and the predictive markers of oxaliplatin-induced cytopenia are worthy.
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Affiliation(s)
- Chung-Jen Teng
- Division of Oncology and Hematology, Department of Medicine, National Yang-Ming University Hospital, Yilan, Taiwan
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Koukourakis GV, Zacharias G, Tsalafoutas J, Theodoridis D, Kouloulias V. Capecitabine for locally advanced and metastatic colorectal cancer: A review. World J Gastrointest Oncol 2010; 2:311-21. [PMID: 21160892 PMCID: PMC2999677 DOI: 10.4251/wjgo.v2.i8.311] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2010] [Revised: 07/30/2010] [Accepted: 08/06/2010] [Indexed: 02/05/2023] Open
Abstract
Capecitabine (Xeloda®) is an oral fluoropyrimidine which is produced as a pro-drug of fluorouracil, and shows improved tolerability and intratumor drug concentrations following its tumor-specific conversion to the active drug. We have searched the Pubmed and Cochrane databases from 1980 to 2009 with the purpose of reviewing all available information on Capecitabine, focusing on its clinical effectiveness against colorectal cancer. Special attention has been paid to trials that compared Capecitabine with standard folinic acid (leucovorin, LV)-modulated intravenous 5-fluorouracil (5-FU) bolus regimens in patients with metastatic colorectal cancer. Moreover the efficacy of Capecitabine on metastatic colorectal cancer, either alone or in various combinations with other active drugs such as Irinotecan and Oxaliplatin was also assessed. Finally, neoadjuvant therapy consisting of Capecitabine plus radiation therapy, for locally advanced rectal cancer was analysed. This combination of chemotherapy and radiotherapy has a special role in tumor down staging and in sphincter preservation for lower rectal tumors. Comparative trials have shown that Capecitabine is at least equivalent to the standard LV-5-FU combination in relation to progression-free and overall survival whilst showing a better tolerability profile with a much lower incidence of stomatitis. It is now known that Capecitabine can be combined with other active drugs such as Irinotecan and Oxaliplatin. The combination of Oxaliplatin with Capecitabine represents a new standard of care for metastatic colorectal cancer. Combinating the Capecitabine-Oxaliplatin regimen with promising new biological drugs such as Bevacizumab seems to give a realistic prospect of further improvement in time to progression of metastatic disease. Moreover, preoperative chemo-radiation using oral capecitabine is better tolerated than bolus 5-FU and is more effective in the promotion of both down-staging and sphincter preservation in patients with locally advanced rectal cancer. Finally, the outcomes of recently published trials suggest that capecitabine seems to be more cost effective than other standard treatments for the management of patients with colorectal cancer.
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Affiliation(s)
- Georgios V Koukourakis
- Georgios V Koukourakis, Department of Radiation Oncology, Anticancer Institute of Athens "Saint Savvas", Athens, Greece
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Siemerink EJM, Drenth AFJ, Mulder NH, Plukker JTM, Hospers GAP. Phase II study of oxaliplatin, UFT, and leucovorin in patients with metastatic gastric cancer. Gastric Cancer 2010; 13:95-100. [PMID: 20602196 DOI: 10.1007/s10120-010-0545-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2009] [Accepted: 01/28/2010] [Indexed: 02/07/2023]
Abstract
BACKGROUND The present study evaluated the efficacy and safety of oxaliplatin, UFT, and leucovorin in metastatic gastric cancer. METHODS Patients received intravenous oxaliplatin 130 mg/m(2) on day 1, followed by oral UFT capsules (350 mg/m(2) per day) and leucovorin tablets (90 mg/day), every 8 h, for 14 days, in a 3-week cycle. RESULTS Twenty-three patients (61% with > or = 2 metastatic sites), median age of 60 years (range, 39-69 years) were entered. Based on intention-to-treat analysis, one complete response and seven partial responses were found, resulting in an overall response rate (RR) of 35% (95% confidence interval [CI], 16-54), a median time to progression of 4 months (95% CI, 0.5-7.5), and a median overall survival (OS) of 8 months (95% CI, 4.5-11.5). The 1-year survival rate was 26%. Three patients did not complete the first course of 2 weeks; 1 died suddenly on day 16 with fatal lung embolism; 1 had rapid progressive disease and 1 experienced gastric hemorrhage on day 15 - both these patients withdrew. In the 20 patients assessable for toxicity no grade 4 toxicity occurred, grade 3 toxicity consisted of anemia in 1, diarrhea in 2, and neurotoxicity in 3 patients. No hand-foot syndrome (HFS) occurred. CONCLUSION Oxaliplatin is an effective drug in gastric cancer, but, as previously reported, its feasibility in combination with capecitabine is hampered due to combined hand-foot-based toxicity. The present phase II study of a combination of oxaliplatin with UFT and leucovorin appears to have efficacy and tolerability comparable to two other drug regimens used in gastric cancer, without the HFS problem.
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Affiliation(s)
- Ester J M Siemerink
- Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
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Defining patient outcomes in stage IV colorectal cancer: a prospective study with baseline stratification according to disease resectability status. Br J Cancer 2010; 102:255-61. [PMID: 20087355 PMCID: PMC2816665 DOI: 10.1038/sj.bjc.6605508] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Background: Stage IV colorectal cancer encompasses a broad patient population in which both curative and palliative management strategies may be used. In a phase II study primarily designed to assess the efficacy of capecitabine and oxaliplatin, we were able to prospectively examine the outcomes of patients with stage IV colorectal cancer according to the baseline resectability status. Methods: At enrolment, patients were stratified into three subgroups according to the resectability of liver disease and treatment intent: palliative chemotherapy (subgroup A), conversion therapy (subgroup B) or neoadjuvant therapy (subgroup C). All patients received chemotherapy with capecitabine 2000 mg m–2 on days 1–14 and oxaliplatin 130 mg m–2 on day 1 repeated every 3 weeks. Imaging was repeated every four cycles where feasible liver resection was undertaken after four or eight cycles of chemotherapy. Results: Of 128 enrolled patients, 74, 22 and 32 were stratified into subgroups A, B and C, respectively. Attempt at curative liver resection was undertaken in 10 (45%) patients in subgroup B and 19 (59%) in subgroup C. The median overall survival was 14.6, 24.5 and 52.9 months in subgroups A, B and C, respectively. For patients in subgroups B and C who underwent an attempt at curative resection, 3-year progression-free survival was 10% in subgroup B and 37% for subgroup C. Conclusions: This prospective study shows the wide variation in outcome according to baseline resectability status and highlights the potential clinical value of a modified staging system to distinguish between these patient subgroups.
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Molassiotis A, Brearley S, Saunders M, Craven O, Wardley A, Farrell C, Swindell R, Todd C, Luker K. Effectiveness of a Home Care Nursing Program in the Symptom Management of Patients With Colorectal and Breast Cancer Receiving Oral Chemotherapy: A Randomized, Controlled Trial. J Clin Oncol 2009; 27:6191-8. [DOI: 10.1200/jco.2008.20.6755] [Citation(s) in RCA: 100] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Purpose To assess the effectiveness of a symptom-focused home care program in patients with cancer who were receiving oral chemotherapy in relation to toxicity levels, anxiety, depression, quality of life, and service utilization. Patients and Methods A randomized, controlled trial was carried out with 164 patients with a diagnosis of colorectal (n = 110) and breast (n = 54) cancers who were receiving oral capecitabine. Patients were randomly assigned to receive either a home care program by a nurse or standard care for 18 weeks (ie, six cycles of chemotherapy). Toxicity assessments were carried out weekly for the duration of the patients' participation in the trial, and validated self-report tools assessed anxiety, depression, and quality of life. Results Significant improvements were observed in the home care group in relation to the symptoms of oral mucositis, diarrhea, constipation, nausea, pain, fatigue (first four cycles), and insomnia (all P < .05). This improvement was most significant during the initial two cycles. Unplanned service utilization, particularly the number of inpatient days (57 v 167 days; P = .02), also was lower in the home care group. Conclusion A symptom-focused home care program was able to assist patients to manage their treatment adverse effects more effectively than standard care. It is imperative that patients receiving oral chemotherapy are supported with such programs, particularly during initial treatment cycles, to improve their treatment and symptom experiences.
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Affiliation(s)
- Alex Molassiotis
- From the School of Nursing, Midwifery, and Social Work, University of Manchester; and Departments of Clinical Oncology, Medical Oncology, and Nursing Administration; and Clinical Trials Unit, Christie Hospital National Health Service Foundation Trust, Manchester, United Kingdom
| | - Sarah Brearley
- From the School of Nursing, Midwifery, and Social Work, University of Manchester; and Departments of Clinical Oncology, Medical Oncology, and Nursing Administration; and Clinical Trials Unit, Christie Hospital National Health Service Foundation Trust, Manchester, United Kingdom
| | - Mark Saunders
- From the School of Nursing, Midwifery, and Social Work, University of Manchester; and Departments of Clinical Oncology, Medical Oncology, and Nursing Administration; and Clinical Trials Unit, Christie Hospital National Health Service Foundation Trust, Manchester, United Kingdom
| | - Olive Craven
- From the School of Nursing, Midwifery, and Social Work, University of Manchester; and Departments of Clinical Oncology, Medical Oncology, and Nursing Administration; and Clinical Trials Unit, Christie Hospital National Health Service Foundation Trust, Manchester, United Kingdom
| | - Andrew Wardley
- From the School of Nursing, Midwifery, and Social Work, University of Manchester; and Departments of Clinical Oncology, Medical Oncology, and Nursing Administration; and Clinical Trials Unit, Christie Hospital National Health Service Foundation Trust, Manchester, United Kingdom
| | - Carole Farrell
- From the School of Nursing, Midwifery, and Social Work, University of Manchester; and Departments of Clinical Oncology, Medical Oncology, and Nursing Administration; and Clinical Trials Unit, Christie Hospital National Health Service Foundation Trust, Manchester, United Kingdom
| | - Ric Swindell
- From the School of Nursing, Midwifery, and Social Work, University of Manchester; and Departments of Clinical Oncology, Medical Oncology, and Nursing Administration; and Clinical Trials Unit, Christie Hospital National Health Service Foundation Trust, Manchester, United Kingdom
| | - Chris Todd
- From the School of Nursing, Midwifery, and Social Work, University of Manchester; and Departments of Clinical Oncology, Medical Oncology, and Nursing Administration; and Clinical Trials Unit, Christie Hospital National Health Service Foundation Trust, Manchester, United Kingdom
| | - Karen Luker
- From the School of Nursing, Midwifery, and Social Work, University of Manchester; and Departments of Clinical Oncology, Medical Oncology, and Nursing Administration; and Clinical Trials Unit, Christie Hospital National Health Service Foundation Trust, Manchester, United Kingdom
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Shibata SI, Doroshow JH, Frankel P, Synold TW, Yen Y, Gandara DR, Lenz HJ, Chow WA, Leong LA, Lim D, Margolin KA, Morgan RJ, Somlo G, Newman EM. Phase I trial of GTI-2040, oxaliplatin, and capecitabine in the treatment of advanced metastatic solid tumors: a California Cancer Consortium Study. Cancer Chemother Pharmacol 2009; 64:1149-55. [PMID: 19322566 PMCID: PMC3046108 DOI: 10.1007/s00280-009-0977-x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2008] [Accepted: 03/03/2009] [Indexed: 12/27/2022]
Abstract
BACKGROUND GTI-2040 is a 20-mer antisense oligonucleotide targeting the mRNA of ribonucleotide reductase M2. It was combined with oxaliplatin and capecitabine in a phase I trial in patients with advance solid tumors based on previous studies demonstrating potentiation of chemotherapy with ribonucleotide reductase inhibitors. METHODS Patients at least 18 years of age with advanced incurable solid tumors and normal organ function as well as a Karnofsky performance status of > or =60% were eligible. One prior chemotherapy regimen for advanced disease or relapse within 12 months of adjuvant chemotherapy was required. Patients could have received prior fluoropyrimidines, including capecitabine, but not oxaliplatin. Treatment cycles were 21 days. In each cycle, GTI-2040 was given as a continuous intravenous infusion over 14 days, oxaliplatin as a 2-h intravenous infusion on day 1, and capecitabine orally twice a day for 14 days. In cycle 1 only, oxaliplatin and capecitabine were started on day 2 to allow ribonucleotide reductase mRNA levels to be measured with and without oxaliplatin and capecitabine. Doses were escalated in cohorts of three patients using a standard 3 + 3 design until the maximum tolerated dose was established, defined as no more than one first-cycle dose-limiting toxicity among six patients treated at a given dose level. RESULTS The maximum tolerated dose was estimated to be the combination of GTI-2040 3 mg/kg per day for 14 days, capecitabine 600 mg/m(2) twice daily for 14 days, and oxaliplatin 100 mg/m(2) every 21 days. Dose-limiting toxicities were hematologic. GTI-2040 pharmacokinetics, obtained at steady-state on days 7 and 14, showed the high inter-patient variability previously reported. Two of six patients had stable disease at the maximum tolerated dose and one patient, with heavily pre-treated non-small cell lung cancer, had a partial response at a higher dose level. In samples from a limited number of patients, there was no clear decrease in ribonucleotide reductase expression in peripheral blood mononuclear cells during treatment. CONCLUSION A combination of GTI-2040, capecitabine and oxaliplatin is feasible in patients with advanced solid tumors.
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Affiliation(s)
- Stephen I Shibata
- Department of Medical Oncology, City of Hope Comprehensive Cancer Center, 1500 E. Duarte Road, Duarte, CA 91010, USA.
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Cathomas R, Köberle D, Ruhstaller T, Mayer G, Räss A, Mey U, von Moos R. Heated (37 degrees C) oxaliplatin infusion in combination with capecitabine for metastatic colorectal carcinoma: can it reduce neuropathy? Support Care Cancer 2009; 18:1263-70. [PMID: 19756772 DOI: 10.1007/s00520-009-0740-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2009] [Accepted: 08/31/2009] [Indexed: 10/20/2022]
Abstract
BACKGROUND/PURPOSE Oxaliplatin-associated neuropathy remains a dose-limiting toxicity of the standard chemotherapy regimen of oxaliplatin and capecitabine for metastatic colorectal cancer. No preventive strategy has definitively been established. Because this neuropathy is triggered by cold, we hypothesized that infusing oxaliplatin at 37 degrees C might reduce neuropathy. METHODS In this open-label pilot feasibility trial, patients with no prior chemotherapy for metastatic colorectal cancer were included. Treatment consisted of capecitabine 1,000 mg/m(2) bid on days 1-14 and oxaliplatin 130 mg/m2 on day 1 of a 21-day cycle. The oxaliplatin infusion was administered through a fluid-warming device at a constant temperature of 37 degrees C over 2 h. The primary endpoint was feasibility and drug reactions during the infusion. Secondary endpoints included acute and chronic neuropathy as well as response rate. RESULTS Twenty patients were enrolled, and a total of 95 cycles administered. Median cumulative oxaliplatin dose was 735 mg/m(2). Apart from one patient with laryngeal spasm, no other infusion-related adverse events were observed. Of the patients, 35% reported grade 3/4 acute dysesthesia or paresthesia according to a patients questionnaire. Chronic neuropathy according to NCI CTC v3.0 was observed in 85% (grade 1) and 15% (grade 2), respectively. The overall response rate was 45% (95% CI 23-67%; 5% complete remission; 40% partial remission) and stable disease was achieved in another 30% of patients. CONCLUSION Administration of heated oxaliplatin in combination with capecitabine is feasible and well tolerated without additional toxicity. While we have observed a relatively low rate of chronic cumulative neuropathy with heated oxaliplatin, this procedure appears not promising enough for us to recommend its further clinical evaluation.
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Pfeiffer P, Hahn P, Jensen HA. Short-time infusion of oxaliplatin (Eloxatin) in combination with capecitabine (Xeloda) in patients with advanced colorectal cancer. Acta Oncol 2009; 42:832-6. [PMID: 14968944 DOI: 10.1080/02841860310015894] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Neuropathy exacerbated by exposure to cold is a dose-limiting toxicity of oxaliplatin. The incidence of this side effect is claimed to dependent on infusion rate and therefore a 2-h infusion is often recommended. For practical reasons and for the convenience of the patient, we used XELOX (Xeloda 2000 mg/m2 orally on days 1-14 and oxaliplatin 130 mg/m2 as a 30-min infusion on day 1) in patients with advanced colorectal cancer resistant to irinotecan and 5-fluorouracil. Thirty-four consecutive patients received a median of 5 courses of XELOX. Nine patients obtained partial response (PR) (response rate (RR) 26%), 11 patients no change (NC), 7 patients disease progression (PD) and 7 patients were not evaluable. Median time to progression was 4.7 (2.6-7.6) months and median survival was 7.4 (6.0-11.3) months. Sixteen patients had neuropathy grade 1, four patients grade 2 and two patients grade 3. Short-time infusion of oxaliplatin and capecitabine is an active and convenient second-line regimen with a safety profile similar to that of other oxaliplatin schedules.
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Affiliation(s)
- Per Pfeiffer
- Department of Oncology, Odense University Hospital, Denmark.
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Jensen SA, Lønborg JT, Sørensen JB. Benefits and risks of palliative capecitabine based therapy to elderly patients with advanced colorectal cancer: Danish single centre experiences. Acta Oncol 2009; 45:67-76. [PMID: 16464798 DOI: 10.1080/02841860500375213] [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: 12/14/2022]
Abstract
This study aimed to compare efficacy and toxicity of palliative chemotherapy for elderly and younger colorectal cancer patients. Patients aged 24-69 (n = 203) and 70-82 years (n = 57) with advanced colorectal cancer were consequetively treated with first line capecitabine monotherapy or combined with oxaliplatin (XELOX). The response rates were 37% and 33% (P = 0.61), the median times to progression were 5.5 and 6.0 months (P = 0.84, hazard ratio (HR) 1.09; 95% confidence interval: 0.71-1.68), and median overall survival times were 8.4 and 12.5 months (P = 0.07, HR 1.48; 1.04-2.38) for elderly and younger patients, respectively. Elderly patients had similar frequencies of Common Toxicity Criteria (CTC) grade 3 or 4 toxicity (P > 0.05) and number of treatment courses (P = 0.44), and maintained performance status as well as younger patients (P = 0.68). Palliative capecitabine based therapy for advanced colorectal cancer should be considered also for elderly who are in good performance without major comorbidities.
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Affiliation(s)
- Søren Astrup Jensen
- Department of Oncology, National University Hospital, 9 Blegdamsvej, Copenhagen, DK-2100, Denmark.
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Abstract
Capecitabine is currently the only novel, orally home-administered fluorouracil prodrug. It offers patients more freedom from hospital visits and less inconvenience and complications associated with infusion devices. The drug has been extensively studied in large clinical trials in many solid tumors, including breast cancer, colorectal cancer, gastric cancer, and many others. Furthermore, the drug compares favorably with fluorouracil in patients with such cancers, with a safe toxicity profile, consisting mainly of gastrointestinal and dermatologic adverse effects. Whereas gastrointestinal events and hand-foot syndrome occur often with capecitabine, the tolerability profile is comparatively favorable. Prompt recognition of severe adverse effects is the key to successful management of capecitabine. Ongoing and future clinical trials will continue to examine, and likely expand, the role of capecitabine as a single agent and/or in combination with other anticancer agents for the treatment of gastrointestinal as well as other solid tumors, both in the advanced palliative and adjuvant settings. The author summarizes the current data on the role of capecitabine in the management of gastrointestinal cancers.
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Köhne CH, Folprecht G, Goldberg RM, Mitry E, Rougier P. Chemotherapy in elderly patients with colorectal cancer. Oncologist 2008; 13:390-402. [PMID: 18448553 DOI: 10.1634/theoncologist.2007-0043] [Citation(s) in RCA: 82] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Significant advancements in chemotherapy for metastatic colorectal cancer (mCRC) have been achieved over the past decade, and the median overall survival duration is now close to 24 months with appropriate treatment. The most widely recommended chemotherapy regimens are based on the use of irinotecan or oxaliplatin in combination with 5-fluorouracil and leucovorin; some data suggest further benefit with the addition of the targeted agents bevacizumab or cetuximab. Colorectal cancer primarily affects the elderly; however, much of the defining clinical research in this field has excluded subjects of advanced age or with a poor performance status, making it difficult for clinicians to interpret current treatment paradigms for their older patients. Most clinical trials that have included elderly patients document similar survival rates and toxicity profiles to those seen in younger patients. Moreover, survey data suggest that >70% of elderly patients with cancer are willing to undergo strong, palliative chemotherapy. While these findings suggest that age itself should not determine candidacy for chemotherapy, it is important to note the great heterogeneity of the elderly population with regard to overall health, independence, and performance status. The use of a comprehensive geriatric assessment is recommended to evaluate chemotherapy appropriateness. The management of frail elderly patients and those with a short life expectancy should be focused on palliation, while fit elderly patients can receive aggressive therapy in a similar fashion to younger patients.
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Affiliation(s)
- Claus-Henning Köhne
- Klinik für Onkologie/Hämatologie, Klinikum Oldenburg, Dr.-Eden-Str. 10, 26133 Oldenburg, Germany.
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Rothenberg ML, Cox JV, Butts C, Navarro M, Bang YJ, Goel R, Gollins S, Siu LL, Laguerre S, Cunningham D. Capecitabine plus oxaliplatin (XELOX) versus 5-fluorouracil/folinic acid plus oxaliplatin (FOLFOX-4) as second-line therapy in metastatic colorectal cancer: a randomized phase III noninferiority study. Ann Oncol 2008; 19:1720-1726. [PMID: 18550577 DOI: 10.1093/annonc/mdn370] [Citation(s) in RCA: 154] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND To demonstrate the noninferiority of capecitabine plus oxaliplatin (XELOX) versus 5-fluorouracil/folinic acid and oxaliplatin (FOLFOX-4) as second-line therapy in patients with metastatic colorectal cancer after prior irinotecan-based chemotherapy. PATIENTS AND METHODS A total of 627 patients were randomly assigned to receive XELOX (n = 313) or FOLFOX-4 (n = 314) following disease progression/recurrence or intolerance to irinotecan-based chemotherapy. The primary end point was progression-free survival (PFS). RESULTS PFS for XELOX was noninferior to FOLFOX-4 [hazard ratio (HR) = 0.97; 95% confidence interval (CI) 0.83-1.14] in the intention-to-treat (ITT) population. Median PFS was 4.7 months with XELOX versus 4.8 months with FOLFOX-4. The robustness of the primary analysis was supported by multivariate and subgroup analyses. Median overall survival in the ITT population was 11.9 months with XELOX versus 12.5 months with FOLFOX-4 (HR = 1.02; 95% CI 0.86-1.21). Treatment-related grade 3/4 adverse events occurred in 50% of XELOX- and 65% of FOLFOX-4-treated patients. Whereas grade 3/4 neutropenia (35% versus 5% with XELOX) and febrile neutropenia (4% versus < 1%) were more common with FOLFOX-4, grade 3/4 diarrhea (19% versus 5% with FOLFOX-4) and grade 3 hand-foot syndrome (4% versus < 1%) were more common with XELOX. CONCLUSION XELOX is noninferior to FOLFOX-4 when administered as second-line treatment in patients with metastatic colorectal cancer.
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Affiliation(s)
- M L Rothenberg
- Division of Hematology/Oncology, Vanderbilt-Ingram Cancer Center, Nashville, TN 37232-6307, USA.
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Saif MW, Katirtzoglou NA, Syrigos KN. Capecitabine: an overview of the side effects and their management. Anticancer Drugs 2008; 19:447-64. [PMID: 18418212 DOI: 10.1097/cad.0b013e3282f945aa] [Citation(s) in RCA: 69] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Xeloda (capecitabine), a thymidine phosphorylase activated fluoropyrimidine carbamate, is currently the only universally approved orally administered 5-fluorouracil (5-FU) prodrug. It belongs to a newer generation of orally administered fluoropyrimidines. It has been developed because of the clinical need for efficient, tolerable and convenient agents, which do not require continuous infusion. Capecitabine is not a cytotoxic drug in itself, but via a three-step enzymatic cascade, it is converted to 5-FU mainly within human cancer cells. While the drug compares favorably with 5-FU in patients with advanced or metastatic colorectal cancer and pretreated breast cancer, it also has an improved toxicity profile, mainly of gastrointestinal and dermatologic effects with a significantly lower incidence of grade 3/4 myelotoxicity compared with infusional 5-FU-based chemotherapy. Capecitabine's selective activation within the tumor allows for less systemic toxicity events. A gradient of fluoropyrimidine toxicity is observed: high in the US and low in East Asia. In addition, there is a discrepancy in tolerance of dose among patients treated in the US vs. Europe. Although patients can take the drug orally in the convenience of their own home, the key to successful management of capecitabine is the clinician's awareness of its severe, but low in incidence, adverse effects, and the patients' education, emphasizing compliance with the treatment plan, prevention and timely recognition of its toxicities.
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Affiliation(s)
- Muhammad Wasif Saif
- Medical Oncology, Yale University School of Medicine, Section of Medical Oncology, New Haven, Connecticut 06520, USA.
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Koukourakis GV, Kouloulias V, Koukourakis MJ, Zacharias GA, Zabatis H, Kouvaris J. Efficacy of the oral fluorouracil pro-drug capecitabine in cancer treatment: a review. Molecules 2008; 13:1897-922. [PMID: 18794792 PMCID: PMC6245068 DOI: 10.3390/molecules13081897] [Citation(s) in RCA: 50] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2008] [Revised: 08/15/2008] [Accepted: 08/25/2008] [Indexed: 12/12/2022] Open
Abstract
Capecitabine (Xeloda) was developed as a pro-drug of fluorouracil (FU), with the aim of improving tolerability and intratumor drug concentrations through its tumorspecific conversion to the active drug. The purpose of this paper is to review the available information on capecitabine, focusing on its clinical effectiveness against various carcinomas. Identification of all eligible English trails was made by searching the PubMed and Cochrane databases from 1980 to 2007. Search terms included capecitabine, Xeloda and cancer treatment. Nowadays, FDA has approved the use of capecitabine as a first line therapy in patients with metastatic colorectal cancer when single-agent fluoropyrimidine is preferred. The drug is also approved for use as a single agent in metastatic breast cancer patients who are resistant to both anthracycline and paclitaxel-based regimens or when further anthracycline treatment is contraindicated. It is also approved in combination with docetaxel after failure of prior anthracycline-based chemotherapy. In patients with prostate, pancreatic, renal cell and ovarian carcinomas, capecitabine as a single-agent or in combination with other drugs has also shown benefits. Improved tolerability and comparable efficacy, compared with the intravenous FU/LV combination, in addition to its oral administration, make capecitabine an attractive option for the treatment of several types of carcinomas.
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Affiliation(s)
- Georgios V. Koukourakis
- Attikon University Hospital of Athens, 2 Radiology Department, Radiation Therapy Unit, Medical School of Athens, Greece; Emails: (Koukourakis); (Kouloulias)
| | - Vassilios Kouloulias
- Attikon University Hospital of Athens, 2 Radiology Department, Radiation Therapy Unit, Medical School of Athens, Greece; Emails: (Koukourakis); (Kouloulias)
| | | | | | - Haralabos Zabatis
- Saint Savvas Anticancer Institute of Athens, 1 Radiation Therapy Unit Athens Greece;
| | - John Kouvaris
- Aretaieion University Hospital, 1 Radiology Department, Radiation Therapy Unit, Medical School of Athens, Greece;
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Comella P, Massidda B, Filippelli G, Farris A, Natale D, Barberis G, Maiorino L, Palmeri S, Cannone M, Condemi G. Randomised trial comparing biweekly oxaliplatin plus oral capecitabine versus oxaliplatin plus i.v. bolus fluorouracil/leucovorin in metastatic colorectal cancer patients: results of the Southern Italy Cooperative Oncology study 0401. J Cancer Res Clin Oncol 2008; 135:217-26. [PMID: 18719941 DOI: 10.1007/s00432-008-0454-7] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2008] [Accepted: 08/05/2008] [Indexed: 12/27/2022]
Abstract
PURPOSE Oxaliplatin combined with either fluorouracil/leucovorin (OXAFAFU) or capecitabine (OXXEL) has a demonstrated activity in metastatic colorectal cancer patients. We aimed at comparing these two regimens in terms of response rate (RR), safety, progression-free survival (PFS), and quality of life (QoL) of patients. METHODS A total of 322 patients with metastatic colorectal cancer were randomized to receive biweekly: oxaliplatin 100 mg/m(2) i.v. on day 1, capecitabine 1,000 mg/m(2) orally twice daily from day 1 to day 11 (OXXEL); or oxaliplatin 85 mg/m(2) i.v. on day 1; 6S-leucovorin 250 mg/m(2) i.v. and fluorouracil 850 mg/m(2) i.v. on day 2 (OXAFAFU). RESULTS Eleven complete and 42 partial responses were registered with OXXEL (RR = 34%); six complete and 48 partial responses were obtained with OXAFAFU (RR = 33%) (P = 0.999). Severe adverse events were less frequent (32 vs. 43%) with OXXEL, which also reduced the occurrence of severe neutropenia (10 vs. 27%) and febrile neutropenia (6 vs. 13%), but produced more gastric side effects (8 vs. 3%) and diarrhea (13 vs. 8%). QoL did not differ across the two arms. Median PFS was 6.6 months in the OXXEL, and 6.5 months in the OXAFAFU arm (HR = 1.12, P = 0.354). Median overall survival was 16.0 and 17.1 months (HR = 1.01, P = 0.883). CONCLUSIONS OXXEL and OXAFAFU regimens were equally active in metastatic colorectal cancer. The choice should be based on patient preference and on pharmacoeconomic evaluations.
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Affiliation(s)
- Pasquale Comella
- Department of Medical Oncology, National Tumour Institute, Via M. Semmola, 80100, Naples, Italy.
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Lee JJ, Chu E. Update on clinical data combining capecitabine with targeted agents in newly diagnosed colorectal cancer. Clin Colorectal Cancer 2008; 7 Suppl 1:S16-20. [PMID: 18361802 DOI: 10.3816/ccc.2008.s.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Colorectal cancer (CRC) is a worldwide public health problem, with nearly 800,000 new cases diagnosed each year, resulting in approximately 500,000 deaths. When advanced metastatic disease is diagnosed, CRC is associated with a poor prognosis, and 5-year survival rates are in the range of 5%-8%. Chemotherapy has been the mainstay approach for patients with advanced CRC. For nearly 40 years, the main drug used for this disease was the fluoropyrimidine 5-fluorouracil (5-FU). Significant advances have been made in chemotherapy treatment options for patients with metastatic disease, such that improvements in 2-year survival are now being reported with median survival rates of 21 months to 24 months. Over the past 10 years, 3 new cytotoxic chemotherapy agents have been approved by the FDA for metastatic CRC. These compounds include the topoisomerase I inhibitor irinotecan, the third-generation platinum analogue oxaliplatin, and the oral fluoropyrimidine capecitabine. Since 2004, 3 novel biologic agents have been approved by the FDA, and they include the anti-epidermal growth factor receptor antibodies cetuximab and panitumumab and the anti-vascular endothelial growth factor bevacizumab. The oral fluoropyrimidine capecitabine has been effectively and safely combined with irinotecan (CAPIRI) and/or oxaliplatin (CAPOX). Three randomized phase III studies have now shown that CAPOX is equivalent to FOLFOX (5-FU/leucovorin/oxaliplatin)-based regimens. Significant interest has centered around combining capecitabine-based cytotoxic regimens with the biologic agents, and specifically, bevacizumab and cetuximab. This review will update the current status of these capecitabine-based combination regimens.
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Affiliation(s)
- James J Lee
- Section of Medical Oncology, Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06520, USA
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Combined portal vein embolization and neoadjuvant chemotherapy as a treatment strategy for resectable hepatic colorectal metastases. Ann Surg 2008; 247:451-5. [PMID: 18376189 DOI: 10.1097/sla.0b013e31815ed693] [Citation(s) in RCA: 146] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVES The objectives of this study are 1) to determine whether the future liver remnant will grow after portal vein embolization (PVE) in patients with colon cancer on concurrent chemotherapy and 2) to determine whether recovery after extended hepatectomy is improved after PVE. PURPOSE Neoadjuvant chemotherapy followed by hepatic resection is an increasingly used therapeutic strategy for curative treatment for colorectal metastases. However, such chemotherapy may result in steatosis, liver damage, and compromised liver regeneration and recovery. This study aims to determine whether PVE can be used during neoadjuvant therapy to enhance growth of future residual liver and to improve postoperative recovery. METHODS From September 1999 to September 2004, 100 patients with colorectal metastases to the liver were subjected to PVE as preparation for extended hepatic resection, 43 of whom were embolized during neoadjuvant chemotherapy. Liver growth was examined by computed tomography volumetric analysis. Clinical outcomes of the 71 patients subsequently resected were compared with 100 consecutive patients subjected to extended resection without PVE (controls). RESULTS After a median wait of 30 +/- 2 days after PVE, patients on neoadjuvant chemotherapy experienced a median contralateral (nonembolized) liver growth of 22% +/- 3% compared with 26% +/- 3% for those without chemotherapy (P = NS). The number of patients with <5% growth was also similar: 4 of 43 versus 6 of 57 (P = NS). Comparison of patients resected after PVE to a simultaneous cohort of 100 consecutive patients subjected to extended resection without prior PVE demonstrated a lower fresh frozen plasma requirement (P = 0.01), a lower peak bilirubin (P = 0.002), and a shorter length of stay (P = 0.03). Mortality was similar (0% vs. 2%). CONCLUSIONS Liver growth occurs after PVE even when cytotoxic chemotherapy is administered. No major complications occurred with PVE. Patients requiring major hepatic resection should be considered for PVE during neoadjuvant chemotherapy to improve subsequent recovery after resection.
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Borner M, Koeberle D, Von Moos R, Saletti P, Rauch D, Hess V, Trojan A, Helbling D, Pestalozzi B, Caspar C, Ruhstaller T, Roth A, Kappeler A, Dietrich D, Lanz D, Mingrone W. Adding cetuximab to capecitabine plus oxaliplatin (XELOX) in first-line treatment of metastatic colorectal cancer: a randomized phase II trial of the Swiss Group for Clinical Cancer Research SAKK. Ann Oncol 2008; 19:1288-1292. [PMID: 18349029 DOI: 10.1093/annonc/mdn058] [Citation(s) in RCA: 102] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND To determine the activity and tolerability of adding cetuximab to the oxaliplatin and capecitabine (XELOX) combination in first-line treatment of metastatic colorectal cancer (MCC). PATIENTS AND METHODS In a multicenter two-arm phase II trial, patients were randomized to receive oxaliplatin 130 mg/m(2) on day 1 and capecitabine 1000 mg/m(2) twice daily on days 1-14 every 3 weeks alone or in combination with standard dose cetuximab. Treatment was limited to a maximum of six cycles. RESULTS Seventy-four patients with good performance status entered the trial. Objective partial response rates after external review and radiological confirmation were 14% and 41% in the XELOX and in the XELOX + Cetuximab arm, respectively. Stable disease has been observed in 62% and 35% of the patients, with 76% disease control in both arms. Cetuximab led to skin rash in 65% of the patients. The median overall survival was 16.5 months for arm A and 20.5 months for arm B. The median time to progression was 5.8 months for arm A and 7.2 months for arm B. CONCLUSION Differences in response rates between the treatment arms indicate that cetuximab may improve outcome with XELOX. The correct place of the cetuximab, oxaliplatin and fluoropyrimidine combinations in first-line treatment of MCC has to be assessed in phase III trials.
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Affiliation(s)
- M Borner
- Institute of Medical Oncology, Inselspital, Bern, Switzerland.
| | - D Koeberle
- Institute of Medical Oncology, Inselspital, Bern, Switzerland
| | - R Von Moos
- Institute of Medical Oncology, Inselspital, Bern, Switzerland
| | - P Saletti
- Institute of Medical Oncology, Inselspital, Bern, Switzerland
| | - D Rauch
- Institute of Medical Oncology, Inselspital, Bern, Switzerland
| | - V Hess
- Institute of Medical Oncology, Inselspital, Bern, Switzerland
| | - A Trojan
- Institute of Medical Oncology, Inselspital, Bern, Switzerland
| | - D Helbling
- Institute of Medical Oncology, Inselspital, Bern, Switzerland
| | - B Pestalozzi
- Institute of Medical Oncology, Inselspital, Bern, Switzerland
| | - C Caspar
- Institute of Medical Oncology, Inselspital, Bern, Switzerland
| | - T Ruhstaller
- Institute of Medical Oncology, Inselspital, Bern, Switzerland
| | - A Roth
- Institute of Medical Oncology, Inselspital, Bern, Switzerland
| | - A Kappeler
- Institute of Medical Oncology, Inselspital, Bern, Switzerland
| | - D Dietrich
- Institute of Medical Oncology, Inselspital, Bern, Switzerland
| | - D Lanz
- Institute of Medical Oncology, Inselspital, Bern, Switzerland
| | - W Mingrone
- Institute of Medical Oncology, Inselspital, Bern, Switzerland
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- Institute of Medical Oncology, Inselspital, Bern, Switzerland
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Moosmann N, Heinemann V. Cetuximab plus XELIRI or XELOX for First-Line Therapy of Metastatic Colorectal Cancer. Clin Colorectal Cancer 2008; 7:110-7. [DOI: 10.3816/ccc.2008.n.015] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Comella P, Casaretti R, Sandomenico C, Avallone A, Franco L. Capecitabine, Alone and in Combination, in the Management of Patients with Colorectal Cancer. Drugs 2008; 68:949-61. [DOI: 10.2165/00003495-200868070-00005] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
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Abstract
The treatment of colorectal cancer has become increasingly complex over recent years. With the emergence of new chemotherapy drugs and targeted agents, there has been great improvement in the prognosis of patients with metastatic colorectal cancer. This review summarises the evidence supporting the use of combination chemotherapy with oxaliplatin and/or irinotecan with fluorouracil (5-FU) for the treatment of colorectal cancer and outlines the pivotal trials. Phase III trials have demonstrated the superiority of combination chemotherapy over single-agent 5-FU, but the optimal sequencing and combination of treatment is yet to be determined. Oral fluoropyrimidine derivatives have been shown to be equivalent to bolus 5-FU treatment and these offer another option for the treatment of colorectal cancer, but further studies are required to evaluate their use with irinotecan and oxaliplatin. The use of newer targeted therapies, such as bevacizumab and cetuximab, alone and in combination with chemotherapy are discussed, and the most recent data supporting their use is outlined. Bevacizumab-containing regimens have been shown to be superior to those without for the first-line treatment of colorectal cancer, and cetuximab has demonstrated activity in combination with chemotherapy in both the first- and second-line setting. Other targeted agents, such as vatalanib and panitumumab, are discussed and early clinical studies with these agents show promising results.
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Affiliation(s)
- Ruth E Board
- Department of Medical Oncology, Cancer Research UK, Christie Hospital, Manchester, UK.
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