Originally published as JCO Early Release 10.1200/JCO.2006.09.8467 on June 4 2007

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Phase III Study of Capecitabine Plus Oxaliplatin Compared With Continuous-Infusion Fluorouracil Plus Oxaliplatin As First-Line Therapy in Metastatic Colorectal Cancer: Final Report of the Spanish Cooperative Group for the Treatment of Digestive Tumors Trial

Eduardo Díaz-Rubio, Jose Tabernero, Auxiliadora Gómez-España, Bartomeu Massutí, Javier Sastre, Manuel Chaves, Alberto Abad, Alfredo Carrato, Bernardo Queralt, Juan José Reina, Joan Maurel, Encarnación González-Flores, Jorge Aparicio, Fernando Rivera, Ferrán Losa, Enrique Aranda

From the Department of Medical Oncology, Hospital Clinico Universitario San Carlos, Madrid; Hospital Vall d’Hebrón, University Barcelona; Hospital Clinic; Hospital Hospitalet, Barcelona; Hospital Reina Sofia, Córdoba; Hospital General, Alicante; Hospital Virgen Rocio, Sevilla; Hospital Germans Trias i Pujol, Badalona; Hospital Universitario Elche, Alicante; ICO, Girona; Hospital J. Ramón Jimenez, Huelva; Hospital Virgen de las Nieves, Granada; Hospital la Fe, Valencia; and the Hospital Marqués Valdecilla, Santander, Spain

Address reprint requests to Eduardo Díaz-Rubio, PhD, Servicio de Oncologia Medica, Hospital Clínico San Carlos, 28040 Madrid, Spain; e-mail: ediazrubio.hcsc{at}salud.madrid.org

Purpose The aim of this phase III trial was to compare the efficacy and safety of capecitabine plus oxaliplatin (XELOX) versus Spanish-based continuous-infusion high-dose fluorouracil (FU) plus oxaliplatin (FUOX) regimens as first-line therapy for metastatic colorectal cancer (MCRC).

Patients and Methods A total of 348 patients were randomly assigned to receive XELOX (oral capecitabine 1,000 mg/m² bid for 14 days plus oxaliplatin 130 mg/m² on day 1 every 3 weeks) or FUOX (continuous-infusion FU 2,250 mg/m² during 48 hours on days 1, 8, 15, 22, 29, and 36 plus oxaliplatin 85 mg/m² on days 1, 15, and 29 every 6 weeks).

Results There were no significant differences in efficacy between XELOX and FUOX arms, which showed, respectively, median time to tumor progression (TTP; 8.9 v 9.5 months; P = .153); median overall survival (18.1 v 20.8 months; P = .145); and confirmed response rate (RR; 37% v 46%; P = .539). The safety profile of the two regimens was similar, although there were lower rates of grade 3/4 diarrhea (14% v 24%) and grade 1/2 stomatitis (28% v 43%), and higher rates of grade 1/2 hyperbilirubinemia (37% v 21%) and grade 1/2 hand-foot syndrome (14% v 5%) with XELOX versus FUOX, respectively.

Conclusion This randomized study shows a similar TTP of XELOX compared with FUOX in the first-line treatment of MCRC, although there was a trend for slightly lower RR and survival. XELOX can be considered as an alternative to FUOX.

published online ahead of print at www.jco.org on June 4, 2007.

Supported by the Treatment of Digestive Tumors (TTD), Madrid, Spain, and by Roche and Sanofi-Aventis.

Presented in part at the 41st Annual Meeting of the American Society of Clinical Oncology, May 13-17, 2005, Orlando, FL; the 42nd Annual Meeting of the American Society of Clinical Oncology, June 2-6, 2005, Atlanta, GA; and the Annual Meeting of the European Society for Medical Oncology, Istanbul, Turkey, September 29-October 3, 2006.

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

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Related Editorial

• Should Capecitabine Replace Infusional Fluorouracil and Leucovorin When Combined With Oxaliplatin in Metastatic Colorectal Cancer?
  Robert J. Mayer
  JCO 2007 25: 4165-4167 [Full Text]

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• Capecitabine Plus Oxaliplatin in Metastatic Colorectal Cancer
  Jim Cassidy
  JCO 2007 25: 5043-5045 [Full Text]

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