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, the LV5FU2 regimen, comprising leucovorin (LV) plus bolus and infusional fluorouracil (5FU) every 2 weeks, was superior to the standard North Central Cancer Treatment Group/Mayo Clinic 5-day bolus 5FU/LV regimen. This phase III 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 with measurable disease were randomized to receive a 2-hour infusion of LV (200 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 together with oxaliplatin 85 mg/m 2 as a 2-hour infusion on day 1. RESULTS Patients allocated to oxaliplatin plus LV5FU2 had significantly longer progression-free survival (median, 9.0 v 6.2 months; P = .0003) and better response rate (50.7% v 22.3%; P = .0001) when compared with the control arm. The improvement in overall survival did not reach significance (median, 16.2 v 14.7 months; P = .12). LV5FU2 plus oxaliplatin gave higher frequencies of National Cancer Institute common toxicity criteria grade 3/4 neutropenia (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 impairment of quality of life (QoL). Survival without disease progression or deterioration in global health status was longer in patients allocated to oxaliplatin treatment ( P = .004). CONCLUSION The LV5FU2-oxaliplatin combination seems beneficial as first-line therapy in advanced colorectal cancer, demonstrating a prolonged progression-free survival with acceptable tolerability and maintenance of QoL.