FLUOROURACIL PLUS RACEMIC LEUCOVORIN VERSUS FLUOROURACIL COMBINED WITH THE PURE L-ISOMER OF LEUCOVORIN FOR THE TREATMENT OF ADVANCED COLORECTAL-CANCER - A RANDOMIZED PHASE-III STUDY

Purpose: To compare the efficacy and toxicity of fluorouracil (FU) and racemic leucovorin (d,l-LV) versus FU combined with the l-isomer of l eucovorin (l-LV) in the treatment of advanced colorectal cancer. Patie nts and Methods: A total of 248 patients with advanced measurable colo rectal cancer previously unexposed to chemotherapy were randomly assig ned to treatment with either FU (400 mg/m(2)/d by intravenous [IV] inf usion for 2 hours) and racemic LV (100 mg/m(2)/d by IV bolus injection ) given for 5 consecutive days, or the combination of FU and the pure I-isomer of LV using the same dose schedule. In both treatment arms, c ourses were administered every 28 days if toxicity allowed for a total of 6 months, unless evidence of tumor progression was documented earl ier. Results: There were no significant differences between the FU/rac emic LV and the FU/l-LV arm in the overall response rate (25% v 32%), duration of response (7.2 v 8.0 months), median rime to progression or death (6.25 v 8.0 months), or median overall survival time (14.5 v 15 .0 months). Except for minor myeloid toxic effects associated with FU/ l-LV, there was also no significant difference in terms of adverse rea ctions, Gastrointestinal symptoms, specifically mucositis and diarrhea , were less frequent and less severe in both treatment arms compared w ith other trials with FU/racemic LV reported in the literature, which might be because of the prolonged administration of FU used in both ar ms. Conclusion: The combination of FU/l-LV produced response rates, re sponse durations, and survival times similar to those with FU/d,I-LV. Biochemical modulation of FU by either pure l-LV or racemic LV thus ap pears to result in equivalent clinical efficacy, (C) 1997 by American Society of Clinical Oncology.