Fluorouracil-alone versus high-dose folinic acid and fluorouracil in advanced colorectal cancer: a randomized trial of the Italian Oncology Group for Clinical Research (GOIRC).
One hundred eighty-one patients with measurable recurrent or metastatic colorectal cancer, who had not received prior chemotherapy, were randomized in a prospective controlled trial to receive 5-fluorouracil (5FU), 13.5 mg/kg, for five days (arm A) or high-dose folinic acid [Cyanamid-Lederle, Italy] (FA), 200 mg/m2, for five days and 5FU, 400 mg/m2 for five days (arm B). The treatments were repeated every four weeks. One hundred fifty-five patients were evaluable for response. The two arms were balanced for all potential prognostic factors studied. The response rate (CR+PR) was 18% in the 5FU arm and 16% in the 5FU plus FA arm. Median duration of response was 56 weeks for 5FU alone and 42 weeks for the combination (p = 0.48). Median time to failure (TTF) was 20 weeks for arm A and 21 for arm B (p = 0.62). Median survival was 62 weeks on the 5FU arm and 53 weeks on the FA plus 5FU arm (p = 0.14). Dose intensity (DI) delivered was the same in both arms. Diarrhea and mucositis were the most frequent adverse reactions in arm B; 20% of the patients in arm A and 38% of those in arm B experienced diarrhea (p = 0.008). Mucositis occurred in 34% of patients in arm A and 42% in arm B (p = 0.04). In general nausea and vomiting were moderate. Hematological toxicity was more severe in patients treated with 5FU alone: 31% in arm A and 14% in arm B developed leukopenia (p = 0.015). In the combination arm one patient died due to gastrointestinal and hematological toxicity after the seventh cycle. This study indicates that, in advanced colorectal cancer, the combination of high-dose FA and 5FU is not superior to 5FU alone when utilized at standard high-dose intensity.
Di Costanzo
F
F
Medical Oncology Service, University Hospital, Terni, Italy.
Bartolucci
R
R
Calabresi
F
F
Sofra
M
M
Marzola
M
M
Belsanti
V
V
Boni
C
C
Bacchi
M
M
D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D002955:Leucovorin / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged
D002955:Leucovorin; D005472:Fluorouracil