The addition of low-dose leucovorin to the combination of 5-fluorouracil- levamisole does not improve survival in the adjuvant treatment of Dukes' C colon cancer. IKN Colon Trial Group

Ann Oncol. 2000 May;11(5):547-52. doi: 10.1023/a:1008351312879.


Purpose: To assess the effect of the addition of leucovorin to the combination of 5-fluorouracil (5-FU)-levamisole on recurrence risk and overall survival in patients after a resection with curative intent of a Dukes' C colon cancer.

Patients and methods: Five hundred patients with Dukes' C colon cancer were randomly assigned to adjuvant treatment for one year with 5-fluorouracil (450 mg/m2 i.v. weekly) and levamisole (150 mg p.o. every two weeks), the C-group or with leucovorin (20 mg/m2 i.v.), 5-fluorouracil and levamisole, the L-group. The median follow-up for patients still alive is 36 months. Four patients were ineligible because of advanced disease at the time of randomisation.

Results: Sixty percent of the patients have completed all courses of chemotherapy. Of the remaining 40% of the patients who did not complete one-year treatment with chemotherapy, 46% discontinued because of toxic and/or emotional reasons. They were equally divided over both treatment arms. The addition of leucovorin increased toxicity (especially mucositis and conjunctivitis) without a significant increase in treatment withdrawal. Five-year disease-free interval (C-group: 49%, L-group: 46%; log-rank test, P = 0.86) and overall survival (C-group: 55%, L-group: 59%, log-rank test: P = 0.96) were very similar in both treatment arms.

Conclusions: The addition of low dose leucovorin to the combination of 5-fluorouracil and levamisole in a 12-month adjuvant therapy for curatively resected Dukes' C colon cancer patients does not improve disease-free interval nor overall survival. The addition of leucovorin to the combination of 5-FU levamisole increases toxicity. Therefore leucovorin 5-FU levamisole is not recommended in a 12 months adjuvant regime of Dukes' C colon cancer.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / pathology
  • Adenocarcinoma / surgery*
  • Adjuvants, Immunologic / administration & dosage*
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Chemotherapy, Adjuvant
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / surgery*
  • Disease-Free Survival
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Leucovorin / administration & dosage
  • Levamisole / administration & dosage*
  • Male
  • Middle Aged
  • Treatment Outcome


  • Adjuvants, Immunologic
  • Levamisole
  • Leucovorin
  • Fluorouracil