Originally published as JCO Early Release 10.1200/JCO.2006.09.2684 on June 4 2007

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Phase III Study of Capecitabine Plus Oxaliplatin Compared With Fluorouracil and Leucovorin Plus Oxaliplatin in Metastatic Colorectal Cancer: A Final Report of the AIO Colorectal Study Group

Rainer Porschen, Hendrik-Tobias Arkenau, Stephan Kubicka, Richard Greil, Thomas Seufferlein, Werner Freier, Albrecht Kretzschmar, Ullrich Graeven, Axel Grothey, Axel Hinke, Wolff Schmiegel, Hans-Joachim Schmoll

From the Hospital Bremen East; Medical School Hanover; University of Salzburg; University Clinic Ulm; Private Oncology Clinic Hildesheim; Robert-Rössle-Clinic; Helios Clinic; Charité Berlin Buch; Hospital Maria Hilf Moenchengladbach; Research Institute WISP Langenfeld; Ruhr-University Bochum; and Martin-Luther-University Halle, Germany; and the Mayo Clinic Rochester, Rochester, MN

Address reprint requests to Rainer Porschen, MD, PhD, Director, Clinic of Internal Medicine, Hospital Bremen East, Zuericher Stasse 40, D-28325 Bremen, Germany; e-mail: rainer.porschen{at}klinikum-bremen-ost.de

Purpose: To compare the use of capecitabine plus oxaliplatin (CAPOX) with infusional fluorouracil (FU)/folinic acid plus oxaliplatin (FUFOX) as first-line therapy for patients with metastatic colorectal cancer (MCRC).

Patients and Methods: A total of 474 patients with MCRC received either CAPOX (capecitabine 1,000 mg/m² bid, days 1 to 14 plus oxaliplatin 70 mg/m² days 1 and 8, repeated every 22 days) ) or FUFOX (oxaliplatin 50 mg/m² followed by leucovorin 500 mg/m² plus FU 2,000 mg/m² as a 22-hour infusion days 1, 8, 15, and 22, repeated every 36 days). The primary end point was progression-free survival (PFS). Secondary end points were response rate (RR), overall survival (OS), time to treatment failure, and toxicity. The study was designed to determine noninferiority for the CAPOX regimen.

Results: Median PFS was 7.1 months in the CAPOX arm and 8.0 months in the FUFOX arm (hazard ratio [HR], 1.17; 95% CI, 0.96 to 1.43; P = .117). Median OS was 16.8 months (CAPOX) and 18.8 months (FUFOX; HR, 1.12; 95% CI, 0.92 to 1.38; P = .26). Overall RRs were 48% for CAPOX (95% CI, 41% to 54%) and 54% for FUFOX (95% CI, 47% to 60%). Both regimens were generally well tolerated, although there was a significantly higher incidence of grade 2/3 hand-foot syndrome (HFS) in the CAPOX arm (P = .028).

Conclusion: CAPOX resulted in a slightly inferior efficacy than FUFOX. With respect to PFS, the best estimate of the HR of 1.17 was within the prespecified equivalence range. However, a relevant inferiority cannot be excluded. Both regimens were generally well tolerated but there was a significantly higher rate of grade 2/3 HFS in the CAPOX arm.

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

Supported by research grants received from Hoffmann-La Roche, Germany, and Sanofi-aventis, Germany.

Presented in part at the 41st Annual Meeting of the American Society of Clinical Oncology, May 13-17, 2005, Orlando, FL, and the Gastrointestinal Cancer Meeting of the American Society of Clinical Oncology, January 26-28, 2006, San Francisco, CA.

R.P. and H.T.A. contributed equally to this study.

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

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]

Related Correspondence

• Comments on Final Report of the AIO Colorectal Cancer Group Study: Fluorouracil/Oxaliplatin Versus Capecitabine/Oxaliplatin
  Thomas Buechele
  JCO 2007 25: 5041-5042 [Full Text]
• Capecitabine Plus Oxaliplatin in Metastatic Colorectal Cancer
  Jim Cassidy
  JCO 2007 25: 5043-5045 [Full Text]

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