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

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/m2) with high-dose (175 mg) or low-dose (25 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, 4,927 patients were enrolled. 1,776 had recurrences and 1,576 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.