Phase II study of fluorouracil and its modulation in advanced colorectal cancer: a Southwest Oncology Group study

J Clin Oncol. 1995 Jun;13(6):1303-11. doi: 10.1200/JCO.1995.13.6.1303.


Purpose: A variety of fluorinated pyrimidine-based regimens for the treatment of disseminated colorectal cancer have been presented in the medical literature. The Southwest Oncology Group designed a screening trial of seven regimens of fluorouracil (5-FU) to assess efficacy and toxicity afforded by biochemical modulation or schedule variations.

Patients and methods: Six hundred twenty patients were entered into this trial between August 1989 and January 1993. Eligible patients were classified as having recurrent or disseminated disease that was measurable or nonmeasurable. All eligible patients were evaluated for toxicity and survival; patients with measurable disease were evaluated for response according to standard criteria.

Results: No regimen achieved a higher response rate than single-agent bolus 5-FU. Eighty-four percent of patients have been monitored until death. The median survival time for the entire cohort is 14 months. Survival hazards ratios showed a positive trend in favor of the unmodulated infusion regimens, while high-grade toxicities occurred more frequently in the 5-FU bolus arms. The major high-grade toxicities were granulocytopenia and diarrhea.

Conclusion: In this trial, no regimen provided substantial improvement relative to 5-FU bolus or single-agent therapy for either response or survival in the treatment of disseminated colorectal cancer. The single-agent infusion regimens demonstrated the most encouraging results with a favorable toxicity profile and a 2-month longer survival duration than 5-FU bolus therapy.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Agranulocytosis / chemically induced
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / therapeutic use
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / mortality
  • Diarrhea / chemically induced
  • Drug Administration Schedule
  • Female
  • Fluorouracil / adverse effects
  • Fluorouracil / therapeutic use*
  • Humans
  • Leucovorin / therapeutic use
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / mortality
  • Phosphonoacetic Acid / analogs & derivatives
  • Phosphonoacetic Acid / therapeutic use
  • Survival Rate


  • Antineoplastic Agents
  • Aspartic Acid
  • sparfosic acid
  • Phosphonoacetic Acid
  • Leucovorin
  • Fluorouracil