A Multicenter Phase-II Study of 5-FU, Leucovorin and Oxaliplatin (FOLFOX6) in Patients with Pretreated Metastatic Colorectal Cancer

Infusional 5-fluorouracil and leucovorin with oxaliplatin is one of the standard regimens for patients with pretreated metastatic colorectal cancer, as well as for first-line chemotherapy. FOLFOX4 has shown its efficacy in pivotal trials, but patients must make twice-weekly hospital visits. FOLFOX6 is a more convenient regimen, requiring a visit once every two weeks. The objective of this study was to evaluate the efficacy and safety profile of FOLFOX6 in Japanese patients with pretreated colorectal cancer. Fifty-one metastatic colorectal cancer patients who failed to respond to first-line chemotherapy were enrolled in the study from April to July 2005. Oxaliplatin, 5-fluorouracil and l-leucovorin were administered every two weeks. Oxaliplatin (100 mg/m(2)) and l-leucovorin (200 mg/m(2)) were given intravenously over 2 h followed by 5-fluorouracil bolus 400 mg/m(2) i.v. and 46-h infusion of 2400 mg/m(2). The primary endpoint was the response rate. Two patients had no measurable lesions and were excluded from the efficacy analysis. Of the 49 eligible patients, one complete response and 6 partial responses were observed, resulting in a response rate (RR) of 14.3% (95% confidence interval: 5.9-27.2%). Median time to treatment failure and progression-free survival was 4.4 and 5.3 months, respectively. Overall survival was 11.4 months. The incidence of grade 2/3 (Debiopharm neurotoxicity criteria) peripheral neuropathy was 41.2%, whereas the overall incidence of grade 3/4 neutropenia was 43.2%. The results of our study suggest that FOLFOX6 had an acceptable profile in terms of both efficacy and safety in previously treated colorectal cancer patients.