Phase III study comparing a semimonthly with a monthly regimen of fluorouracil and leucovorin as adjuvant treatment for stage II and III colon cancer patients:: Final results of GERCOR c96.1

Purpose This randomized, 2 x 2 factorial study compared a semimonthly regimen ( fluorouracil [ FU] and leucovorin [ LV] semi-monthly is LV5FU2) with a monthly regimen of FU and LV ( mFU/LV) as well as 24 weeks versus 36 weeks of each regimen as adjuvant treatment of stage II and III colon cancer. Patients and Methods LV5FU2 was administered semimonthly for 2 days as racemate ( dl) or levogyre ( l-; 200 or 100 mg/m(2)) as a 2-hour infusion, followed by 400 mg/m(2) FU bolus and a 600-mg/m(2) FU 22-hour continuous infusion. FU and LV were administered monthly ( mFU/ LV) for 5 days as dl- or l-LV 15-minute infusion, followed by a 400 mg/m(2) FU 15-minute infusion. The primary end point was disease-free survival ( DFS). Results Between September 1996 and November 1999, 905 patients with stage II ( 43%) and III ( 57%) colon cancer were enrolled. The median follow-up was 6 years. There was no statistically significant difference between mFU/ LV and LV5FU2 in terms of DFS ( 150 v 148 events; hazard ratio [ HR], 1.01; 95% CI, 0.806 to 1.269; P = .94) and overall survival ( OS; 104 v 103 events; HR, 1.02; 95% CI, 0.77 to 1.34; P = .91). No statistical difference was observed between 24 or 36 weeks of chemotherapy. Median survival from metastatic relapse was 24 months. The survival of patients with metastatic relapse ( n = 243) was significantly longer for patients with a longer time from random assignment to relapse ( < 1, 1 to 2, >= 2 years; log-rank test for trend P,.0497). Conclusion DFS and OS were not statistically different between treatment groups and treatment durations. These data confirm the value of LV5FU2 as control arm in the Multicenter International Study of Oxaliplatin/5FU-LV in the Adjuvant Treatment of Colon Cancer and Pan-European Trials in Adjuvant Colon Cancer studies.