A randomized clinical trial with a weekly regimen of 5-fluorouracil with or without folinic acid in advanced gastrointestinal adenocarcinomas: a preliminary report

J Chemother. 1989 Jun;1(3):197-202. doi: 10.1080/1120009x.1989.11738890.


Eighty patients with advanced gastrointestinal tumors (64% with colorectal cancer) entered a phase III prospective randomized study with 5-fluorouracil (5-FU) vs 5-FU + folinic acid (FA) The treatment included 5-FU, 600 mg/m2/week for 6 weeks, given as i.v. bolus alone (arm A), or administered by rapid injection half-way through a one-hour infusion of FA, 200 mg/m2/week for 6 weeks (arm B). Partial remission (PR) was achieved in 1 out of 30 (3%) evaluable patients for 6 months in arm A, and in 10 out of 34 (29%) patients in arm B, with a median duration of 8 months (range 6-17) (comparison of the response rate: P = 0.005). In patients with colorectal cancer the response rate was 5% and 27% in arm A and in arm B respectively (P = 0.06). Two patients, who were resistant to 5-FU alone, achieved PR after treatment with 5-FU + FA. Diarrhea was observed in 14/42 patients (33%) in arm B (grade 1-2 in 10 and grade 3 in 4) and in 2/38 patients (5%) in arm A (P = 0.005). Other side effects such as nausea/vomiting, myelosuppression and stomatitis were infrequent and of mild intensity in both arms. No statistical difference in survival was detected when comparing the two groups (estimated median survival 8 months and 11 months for arm A and arm B respectively). These results seem to indicate that the weekly regimen of 5-FU + FA has a superior response rate compared to 5-FU alone, and that it is well tolerated. However, the advantage is not reflected in overall survival.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Drug Administration Schedule
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Gastrointestinal Neoplasms / drug therapy*
  • Humans
  • Leucovorin / administration & dosage
  • Leucovorin / adverse effects
  • Liver Neoplasms / secondary
  • Lung Neoplasms / secondary
  • Male
  • Middle Aged
  • Pelvic Neoplasms / secondary
  • Prospective Studies
  • Randomized Controlled Trials as Topic


  • Leucovorin
  • Fluorouracil