Efficacy of Oxaliplatin Plus Capecitabine or Infusional Fluorouracil/Leucovorin in Patients With Metastatic Colorectal Cancer: A Pooled Analysis of Randomized Trials

Hendrik-Tobias Arkenau, Dirk Arnold, Jim Cassidy, Eduardo Diaz-Rubio, Jean-Yves Douillard, Howard Hochster, Andrea Martoni, Axel Grothey, Axel Hinke, Wolff Schmiegel, Hans-Joachim Schmoll, Rainer Porschen

From the Royal Marsden Hospital, London and Surrey; Beatson Oncology Centre, Glasgow, United Kingdom; Martin-Luther-University, Halle; WiSP Research Institute, Langenfeld; Ruhr University Bochum; Hospital Bremen East, Bremen, Germany; Hospital Clínico San Carlos Madrid, Spain; Centre R. Gauducheau Saint Herblain, France; New York University School of Medicine, New York, NY; S. Orsola-Malphigi Hospital Bologna, Italy; Mayo Clinic, Rochester, MN

Corresponding author: Hendrik-Tobias Arkenau, MD, Drug Development Unit, Royal Marsden Hospital & Institute of Cancer Research, Downs Road, SM2 5PT Sutton, Surrey, United Kingdom; e-mail: htarkenau@aol.com

Purpose: Six randomized phase II and III trials have investigated the role of oxaliplatin (OX) in combination with capecitabine (CAP) or infusional fluorouracil (FU) in metastatic colorectal cancer. This meta-analysis compared the efficacy of CAP/OX compared with infusional FU/OX.

Patients and Methods: This analysis compared all published CAP/OX versus infusional FU/OX regimens. A total of 3,494 patients (FU, n = 1,737; CAP, n = 1,757) were analyzed for response rate (RR), progression-free (PFS), overall survival (OS), and toxicity.

Results: The fixed-effect pooled estimate for RR showed higher RR for FU-based regimens (Odds ratio [OR] = 0.85; 95% CI, 0.74 to 0.97; P = .02) whereas the analysis of chemotherapy-only trials, excluding the bevacizumab containing NO16966 and TREE 2 trials, led to an OR of 0.74 (95% CI, 0.60 to 0.92; P = .007). However, for PFS (hazard ratio [HR] = 1.04; 95% CI, 0.96 to 1.12; P = .17) and OS (HR = 1.04; 95% CI, 0.95 to 1.12; P = .41) all models suggested similar outcome within the range of noninferiority. Grade 3/4 toxicities (thrombocytopenia—HR = 2.07, 95% CI, 1.42 to 3.03; P < .0002; diarrhea—HR = 1.34; 95% CI, 1.08 to 1.66; P < .0009; and grade 2/3 hand-foot-syndrome [HFS]—HR = 3.54; 95% CI, 2.07 to 6.05; P < .00001) were less prominent with FU-based regimens whereas neutropenia (HR = 0.15; 95% CI, 0.11 to 0.19; P < .00001) was lower in the CAP regimens.

Conclusion: The combination of CAP and OX resulted in lower RR, but this did not affect PFS and OS, which were similar in both treatment arms. The toxicity analysis showed the characteristic toxicity of each of the different FU schedules, with thrombocytopenia and HFS consistently more prominent in the CAP regimens.

published online ahead of print at www.jco.org on November 17, 2008.