Bimonthly high-dose leucovorin, 5-fluorouracil infusion and oxaliplatin (FOLFOX3) for metastatic colorectal cancer resistant to the same leucovorin and 5-fluorouracil regimen

Background. FOLFOX2, a bimonthly regimen of high-dose leucovorin (LV), 48-h our continuous infusion of 5-fluorouracil (5-FU) (LV-5-FU) and oxaliplatin (100 mg/m(2)) produced a high response rate (46%; 95% confidence interval ( 95% CI): 31%-60%) in 5-FU pre-treated patients with metastatic colorectal c ancer. In this phase II study, pre-treated patients were given a lower dose of oxaliplatin to reduce the toxic effects of the regimen. Patients and methods. Thirty patients with advanced colorectal adenocarcino ma and progression while receiving bimonthly LV-5-FU (LV: 500 mg/m(2), 5-FU : 1.5-2 g/m(2)/22 hours, days 1-2; every two weeks), were given the same LV -5-FU schedule with the addition of oxaliplatin (85 mg/m(2)) every two week s (FOLFOX3). Results: The main toxic effects were peripheral neuropathy (90%) with four severe sensitive neuropathies (WHO grade 2: 13%). The response rate was 20% (95% CI: 8%-39%). Median progression-free survival was 26 weeks, median su rvival was 57 weeks from the start of FOLFOX3 and median duration of the re sponse was 37 weeks. Conclusions. Results obtained with FOLFOX3 confirmed the synergy between ox aliplatin and 5-FU in 5-FU-resistant metastatic colorectal cancer. However, the response rate seems to be lower than that obtained with FOLFOX2. Furth er studies to determine the best oxaliplatin dose intensity are in progress .