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

From May 1988 to June 1992, 129 eligible patients suffering from measu rable advanced colorectal cancer were enrolled in a randomized study c omparing bolus fluorouracil plus leucovorin (FU-FA); continuous fluoro uracil infusion (FUcont); FUcont plus cyclophosphamide and mitomycin C (FUMIC). FU-FA consisted of weekly fluorouracil (FUra) bolus (600 mg/ m(2)) 1 hour after the initiation of a 2-hour infusion of 500 mg/m(2) of leucovorin, for 6 weeks every 8 weeks. FUcont patients were planned to receive 400 mg/m(2)/day FUra infusion, for 21 days every 28 days. In FUMIC patients, FUcont was associated with weekly cyclophosphamide bolus (300 mg/m(2)) and monthly mitomycin C bolus (10 mg/m(2)). Qualit y of life was evaluated using six linear analogue scales, completed by the patient. Accrual in the FUMIC arm was stopped after the 25th pati ent 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 sur vival (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 FUco nt arm compared with the FU-FA arm. Toxicity was observed in 62% of th e FUcont patients (grade 3-4: 10%), mainly hand-foot syndrome, diarrhe a, mucositis, and mainly gastrointestinal in 69% of the EU-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 FU cont patients. We conclude that this FUcont schedule, achieving high F Ura dose-intensity, offers significant advantages, in terms of respons e and survival, over weekly FUra plus leucovorin.