Oxaliplatin, leucovorin and fluorouracil in pretreated patients with advanced colorectal cancer.

Preliminary studies suggest synergy between oxaliplatin and fluorouracil (5-FU). To assess this issue, we performed a study in pretreated patients with advanced colorectal cancer (CRC) resistant to leucovorin and 5-FU. Regimen consisted of oxaliplatin day 1, 130 mg/m(2) every two cycles (folfox 1) or 100 mg/m(2)/cycle (folfox 2) or 85 mg/m(2)/cycle (folfox 3) and leucovorin 500 mg/m(2) as a 2-hour infusion, followed by 5-FU 22 h infusion 1.5-2 g/m(2) for two consecutive days every 2 weeks. One hundred and thirteen patients have been treated. One complete response (CR) and 32 partial responses (PRs) were observed for an overall response rate of 29.2%. Sixty-seven patients had prior documented progression while receiving the same schedule of leucovorin and 5-FU than the one used in the folfox regimens, among them 18 had PRs (26.9%). The best response rate was observed in patients treated with the folfox 2 regimen: 41.7%. From start of folfox, median progression-free survival was 6 months and median survival 13 months. Limiting toxicities were peripheral neuropathy and neutropenia. Fifty-four percent of the patients experienced WHO toxicity greater than or equal to grade 3 with the folfox1 regimen, 45% with the folfox2 and 40% with the folfox3 The folfox regimens achieve a high response rate in pretreated patients with CRC. Further studies are needed to determine the best oxaliplatin dose-intensity.