This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Cassidy, J. Articles by Saltz, L. PubMed PubMed Citation Articles by Cassidy, J. Articles by Saltz, L.

Randomized Phase III Study of Capecitabine Plus Oxaliplatin Compared With Fluorouracil/Folinic Acid Plus Oxaliplatin As First-Line Therapy for Metastatic Colorectal Cancer

Jim Cassidy, Stephen Clarke, Eduardo Díaz-Rubio, Werner Scheithauer, Arie Figer, Ralph Wong, Sheryl Koski, Mikhail Lichinitser, Tsai-Shen Yang, Fernando Rivera, Felix Couture, Florin Sirzén, Leonard Saltz

From the Beatson Oncology Centre, Glasgow, United Kingdom; University of Sydney and Sydney Cancer Centre, Sydney, Australia; Hospital Clínico San Carlos, Madrid; Hospital Marques De Valdecilla, Santander, Spain; Vienna University Medical School, Vienna, Austria; Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Cancer Care Manitoba, St Boniface General Hospital, Winnipeg, Manitoba; Cross Cancer Institute, Edmonton, Alberta; CHUQ L'Hotel-Dieu De Quebec, Quebec, Canada; Russian Cancer Research Center, Moscow, Russian Federation; Chang-Gung Memorial Hospital, Taipei, Taiwan; F. Hoffmann-La Roche, Basel, Switzerland; and the Memorial Sloan Kettering Cancer Center, New York, NY

Corresponding author: Jim Cassidy, MD, Glasgow University, Garscube Estate, Switchback Rd, Glasgow, Scotland, G61 1BD; e-mail: j.cassidy{at}beatson.gla.ac.uk

Purpose: To evaluate whether capecitabine plus oxaliplatin (XELOX) is noninferior to fluorouracil. folinic acid, and oxaliplatin (FOLFOX-4) as first-line therapy in metastatic colorectal cancer (MCRC).

Patients and Methods: The initial design of this trial was a randomized, two-arm, noninferiority, phase III comparison of XELOX versus FOLFOX-4. After patient accrual had begun, the trial design was amended in 2003 after bevacizumab phase III data became available. The resulting 2 x 2 factorial design randomly assigned patients to XELOX versus FOLFOX-4, and then to also receive either bevacizumab or placebo. We report here the results of the analysis of the XELOX versus FOLFOX-4 arms. The analysis of bevacizumab versus placebo with oxaliplatin-based chemotherapy is reported separately. The prespecified primary end point for the noninferiority analysis was progression-free survival.

Results: The intent-to-treat population comprised 634 patients from the original two-arm portion of the study, plus an additional 1,400 patients after the start of the amended 2 x 2 design, for a total of 2,034 patients. The median PFS was 8.0 months in the pooled XELOX-containing arms versus 8.5 months in the FOLFOX-4–containing arms (hazard ratio [HR], 1.04; 97.5% CI, 0.93 to 1.16). The median overall survival was 19.8 months with XELOX versus 19.6 months with FOLFOX-4 (HR, 0.99; 97.5% CI, 0.88 to 1.12). FOLFOX-4 was associated with more grade 3/4 neutropenia/granulocytopenia and febrile neutropenia than XELOX, and XELOX with more grade 3 diarrhea and grade 3 hand-foot syndrome than FOLFOX-4.

Conclusion: XELOX is noninferior to FOLFOX-4 as a first-line treatment for MCRC, and may be considered as a routine treatment option for appropriate patients.

Supported by Roche.

Presented in part at the 31st European Society of Medical Oncology Congress, Istanbul, Turkey, September 29- October 3, 2006; the American Society of Clinical Oncology Gastrointestinal Cancers Symposium, Orlando, FL, January 19-21, 2007; and the 43rd Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 1-5, 2007.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

This article has been cited by other articles:

				S. Cowman, J. Stebbing, and M. Tuthill Large bowel perforation associated with capecitabine treatment for breast cancer Ann. Onc., June 18, 2008; (2008) mdn397v1. [Full Text] [PDF]

				M. L. Rothenberg, J. V. Cox, C. Butts, M. Navarro, Y.-J. Bang, R. Goel, S. Gollins, L. L. Siu, S. Laguerre, and D. Cunningham 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. Onc., June 10, 2008; (2008) mdn370v1. [Abstract] [Full Text] [PDF]

				L. B. Saltz, S. Clarke, E. Diaz-Rubio, W. Scheithauer, A. Figer, R. Wong, S. Koski, M. Lichinitser, T.-S. Yang, F. Rivera, et al. Bevacizumab in Combination With Oxaliplatin-Based Chemotherapy As First-Line Therapy in Metastatic Colorectal Cancer: A Randomized Phase III Study J. Clin. Oncol., April 20, 2008; 26(12): 2013 - 2019. [Abstract] [Full Text] [PDF]