Randomized trial comparing monthly low-dose leucovorin and fluorouracil bolus with weekly high-dose 48-hour continuous-infusion fluorouracil for advanced colorectal cancer: a Spanish Cooperative Group for Gastrointestinal Tumor Therapy (TTD) study

Ann Oncol. 1998 Jul;9(7):727-31. doi: 10.1023/a:1008282824860.


Purpose: The objective of this multicenter study was to compare the efficacy and toxicity profiles of a combination of 5-fluorouracil (5-FU) given by bolus injection together with intravenous leucovorin (LV) versus high-dose 5-FU in continuous infusion (CI) in the treatment of advanced colorectal cancer.

Patients and methods: A total of 306 patients were randomized to receive either 5-FU 425 mg/m2 given by bolus injection on days 1-5 plus intravenous (i.v.) LV 20 mg/m2 every four to five weeks or 5-FU 3.5 g/m2/week in a 48-hour CI. Therapy was continued until disease progression. Second-line chemotherapy was allowed in both arms.

Results: The response rates in 306 patients with measurable lesions were 19.2% (modulated arm) and 30.3% (CI arm, P < 0.05). The median progression-free survival times were 23.5 weeks (modulated arm) and 25 weeks (CI arm, P = NS). Median survival times were 42.5 weeks (modulated arm) and 48 weeks (CI arm, P = NS). There were no significant differences in grade 3-4 toxicity profiles but if we consider all grades we observed more mucositis in the modulated arm and more hand-foot syndrome in the CI arm.

Conclusions: In terms of response rate, the continuous infusion regimen was more effective than the modulated regimen. There was no significant difference in survival and time to progression, and none in grade 3-4 toxicity.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antimetabolites, Antineoplastic / administration & dosage*
  • Antimetabolites, Antineoplastic / therapeutic use
  • Colorectal Neoplasms / drug therapy*
  • Drug Administration Schedule
  • Female
  • Fluorouracil / administration & dosage*
  • Fluorouracil / therapeutic use
  • Humans
  • Infusions, Intravenous
  • Injections, Intravenous
  • Leucovorin / administration & dosage*
  • Male
  • Middle Aged
  • Survival Analysis


  • Antimetabolites, Antineoplastic
  • Leucovorin
  • Fluorouracil