Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer

Purpose: In a previous study of treatment for advanced colorectal cancer, t he LV5FU2 regimen, comprising leucovorin (LV) plus bolus and infusional flu orouracil (5FU) every 2 weeks, was superior to the standard North Central C ancer Treatment Group/Mayo Clinic 5-day bolus 5FU/LV regimen. This phase II I study investigated the effect of combining oxaliplatin with LV5FU2, with progression-free survival as the primary end point. Patients and Methods: Four hundred twenty previously untreated patients wit h measurable disease were randomized to receive a 2-hour infusion of LV (20 0 mg/m(2)/d) followed by a 5FU bolus (400 mg/m(2)/d) and 22-hour infusion ( 600 mg/m(2)/d) for 2 consecutive days every 2 weeks, either alone or togeth er with oxaliplatin 85 mg/m(2) as a 2-hour infusion on day 1. Results: Patients allocated to oxaliplatin plus LV5FU2 had significantly lo nger progression-free survival (median, 9.0 v 6.2 months; P = .0003) and be tter response rate (50.7% v 22.3%; P = .0001) when compared with the contro l arm. The improvement in overall survival did not reach significance (medi an, 16.2 v 14.7 months; P = .12). LV5FU2 plus oxaliplatin gave higher frequ encies of National Cancer Institute common toxicity criteria grade 3/4 neut ropenia (41.7% v 5.3% of patients), grade 3/4 diarrhea (11.9% v 5.3%), and grade 3 neurosensory toxicity (18.2% v 0%), but this did not result in impa irment of quality of life (QoL). Survival without disease progression or de terioration in global health status was longer in patients allocated to oxa liplatin treatment (P = .004). Conclusion: The LV5FU2-oxaliplatin combination seems beneficial as first-li ne therapy in advanced colorectal cancer, demonstrating a prolonged progres sion-free survival with acceptable tolerability and maintenance of QoL. (C) 2000 by American Society of Clinical Oncology.