A Randomized Study of Bolus Fluorouracil Plus Folinic Acid Versus 21-Day Fluorouracil Infusion Alone or in Association with Cyclophosphamide and Mitomycin C in Advanced Colorectal Carcinoma

Abstract

From May 1988 to June 1992, 129 eligible patients suffering from measurable advanced colorectal cancer were enrolled in a randomized study comparing bolus fluorouracil plus leucovorin (FU-FA); continuous fluorouracil infusion (FU-cont); FUcont plus cyclophosphamide and mitomycin C (FUMIC). FU-FA consisted of weekly fluorouracil (FUra) bolus (600 mg/m2) 1 hour after the initiation of a 2-hour infusion of 500 mg/m2 of leucovorin, for 6 weeks every 8 weeks. FUcont patients were planned to receive 400 mg/m2/day FUra infusion, for 21 days every 28 days. In FUMIC patients, FUcont was associated with weekly cyclophosphamide bolus (300 mg/m2) and monthly mitomycin C bolus (10 mg/m2). Quality of life was evaluated using six linear analogue scales, completed by the patient. Accrual in the FUMIC arm was stopped after the 25th patient because of toxicity. The response rates were 22 of 48 (45.8%) with FUcont and 13 of 52 (25%) with FU-FA (P = .048). Progression-free survival (median: 8 v 4.4 months; P = .0026) and overall survival (median: 12.9 v 9.6 months; P = .028) were significantly greater for the FUcont arm compared with the FU-FA arm. Toxicity was observed in 62% of the FUcont patients (grade 3-4: 10%), mainly hand-foot syndrome, diarrhea, mucositis, and mainly gastrointestinal in 69% of the FU-FA patients (grade 3-4: 11.6%). Linear analogue scales exploring quality of life, available for the first 6 months, gave similar scores in FU-FA and FUcont patients. We conclude that this FUcont schedule, achieving high FUra dose-intensity, offers significant advantages, in terms of response and survival, over weekly FUra plus leucovorin.