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)

Ann Oncol. 1992 May;3(5):371-6. doi: 10.1093/oxfordjournals.annonc.a058209.


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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Colorectal Neoplasms / drug therapy*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Fluorouracil / adverse effects
  • Fluorouracil / therapeutic use*
  • Humans
  • Leucovorin / adverse effects
  • Leucovorin / therapeutic use*
  • Male
  • Middle Aged


  • Leucovorin
  • Fluorouracil