Fluorouracil plus leucovorin as effective adjuvant chemotherapy in curatively resected stage III colon cancer: Results of the trial adjCCA-01

Purpose: Adjuvant postoperative treatment with fluorouracil (5-FU) and leva misole in curatively resected stage III colon cancer significantly reduces the risk of cancer recurrence and improves survival. Biochemical modulation of 5-FU with leucovorin has resulted in increased remission rates in metas tatic colorectal cancer, thus reflecting an increased tumor-cell kill. The impact of 5-FU plus leucovorin on survival and tumor recurrence was analyze d in comparison with the effects of 5-FU plus levamisole in the prospective multicentric trial adjCCA-01. Patients and Methods: Patients with a curatively resected International Uni on Against Cancer stage ill colon cancer were stratified according to T, N, and G category and randomly assigned to receive one of the two adjuvant tr eatment schemes: 5-FU 400 mg/m(2) body-surface area inf intravenously in th e first chemotherapy course, then 450 mg/m(2) x 5 days; 12 cycles, plus leu covorin 100 mg/m(2) (arm A), or 5-FU plus levamisole (Moertel scheme; arm B ). Results: Six hundred eighty (96.9%) of 702 patients enrolled onto this stud y were eligible. After a median follow-up time of 46.5 months, the 5-FU plu s leucovorin combination significantly improved disease-free survival (P = .037) and significantly decreased overall mortality (P = .0089) in comparis on with 5-FU plus levamisole. In a multivariate proportional hazards model, adjuvant chemotherapy emerged as a significant prognostic factor for survi val (P = .0059) and disease-free survival (P = .03). Adjuvant treatment wit h 5-FU plus levamisole as well as with 5-FU plus leucovorin was generally w ell tolerated; only a minority of patients experienced grade 3 and 4 toxici ties. Conclusion: After a curative resect ion of a stage ill colon cancer, adjuva nt treatment with 5-FU plus leucovorin is generally well tolerated and sign ificantly more effective than 5-FU plus levamisole in reducing tumor relaps e and improving survival. (C) 2001 by American Society of Clinical Oncology .