Multicenter phase II study of bimonthly high-dose leucovorin, fluorouracilinfusion, and oxaliplatin for metastatic colorectal cancer resistant to the same leucovorin and fluorouracil regimen

Purpose: To evaluate the objective tumor response rates and toxicities of l eucovorin (LV) plus fluorouracil (5-FU) cancer regimen combined with oxalip latin (85 mg/m(2)) every 2 weeks on metastatic colorectal cancer patients w ith documented proof of progression while on bimonthly LV and 5-FU alone, patients and Methods: One hundred patients were enrolled onto this study an d 97 received the study drugs between October 1995 and December 1996. Eight y-nine patients were eligible for per-protocol efficacy analysis with docum ented proof of progression on one of the following two treatments: LV 500 m g/m(2) and continuous 5-FU infusion 1.5 to 2 g/m(2)/22 hours, days 1 throug h 2 every 2 weeks (FOLFUHD); or LV 200 mg/m(2), bolus 5-FU 400 mg/m2, and c ontinuous 5-FU infusion 600 mg/m(2)/22 hours, days 1 through 2 every 2 week s [LV5FU2). in our study, 40 patients received FOLFUHD + 85 mg/m(2) of oxal iplatin day 1 (FOLFOX3) and 57 patients received LV5FU2 + 85 mg/m(2) of oxa liplatin day 1 (FOLFOX4). Results: Of the 97 patients treated, 20 partial responses were observed (FO LFOX3/4: response Kite, 20.6%; 95% confidence interval, 13% to 31.1%; FOLFO X3: response rate,18.4%; FOLFOX4: response rate, 23.5%). For patients treat ed with FOLFOX3/4, the median response duration for was 7.5 months, and the major toxicities were peripheral neuropathy and neutropenia. The incidence of grade 3 (National Cancer Institute common toxicity criteria) peripheral neuropathy was 20.6%; whereas the overall incidence of grade 3 to 4 neutro penia wets 27.8%, 15%, and 36.9% for FOLFOX3/4, FOLFOX3, and FOLFOX4 respec tively (P = .02). From the start of treatment, median progression-free surv ival was 4.7, 4.6, and 5.1 months for FOLFOX3/4, FOLFOX3, FOLFOX4, respecti vely, and median overall survival was 10.8, 10.6, and 1 1,1 months, respect ively. Conclusion: This phase II study of oxaliplatin at 85 mg/m(2) in combination with bimonthly LV plus 5-FU in patients with colorectal cancer resistant t o LV plus 5-FU atone confirms the enhanced antitumor activity of oxaliplati n in combination with 5-FU. (C) 1999 by American Society of Clinical Oncolo gy.