Comparison of fluorouracil with additional levamisole, higher-dose folinic acid, or both, as adjuvant chemotherapy for colorectal cancer: a randomised trial

Background Standard adjuvant chemotherapy for colorectal cancer consists of fluorouracil with folinic acid or levamisole. The large QUASAR randomised trial aimed to investigate (in a two x two design) whether use of a higher dose of folinic acid or addition of levamisole to fluorouracil and folinic acid improved survival. Methods Patients with colorectal cancer, without evident residual disease, were randomly assigned fluorouracil (370 mg/m(2)) with high-dose (175 mg) or low-dose (15 mg) L-folinic acid and either active or placebo levamisole. The fluorouracil and folinic acid could be given either as six 5-day courses with 4 weeks between the start of the courses or as 30 once-weekly doses. Levamisole (50 mg) or placebo was given three times daily for 3 days repeated every 2 weeks for 12 courses. The primary endpoint was mortality from any cause. Analyses were by intention to treat. Findings Between 1994 and 1997, 4927 patients were enrolled. 1776 had recurrences and 1576 died. Survival was similar with high-dose and low-dose folinic acid (70.1% vs 71.0% at 3 years; p=0.43), as were 3-year recurrence rates (36.0% vs 35.8%; p=0.94). Survival was worse with levamisole than with placebo (69.4% vs 71.5% at 3 years; p=0.06). and there were more recurrences with the active drug (37.0% vs 34.9% at 3 years; p=0.16). Interpretation The inclusion of levamisole in chemotherapy regimens for colorectal cancer does not delay recurrence or improve survival. Higher-dose folinic acid produced no extra benefit in these regimens over that from low-dose folinic acid. Trials of chemotherapy versus no chemotherapy will show whether these four treatments are equally effective or equally ineffective.