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.

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.