Double-blind randomised trial comparing 5-fluorouracil plus leucovorin to placebo for metastatic colorectal carcinoma

OBJECTIVE: Previous randomised trials of chemotherapy for metastatic colorectal cancer have not concealed the allocation of treatment from participants. Most of these unblinded trials showed improved survival with chemotherapy. This trial used a double-blind design to test the hypothesis that there is no difference between the effect of 5-fluorouracil plus leucovorin and the effect of placebo on the survival of subjects with metastatic colorectal cancer. PATIENTS AND METHODS: In one hospital, 147 subjects with metastatic colorectal cancer were studied from 1989 to 2001. 73 were allocated chemotherapy with 5-fluorouracil plus leucovorin. 74 were allocated placebo. The primary end point was survival after randomization. Secondary end points were performance score, quality of life, serum level of carcinoembryonic antigen (CEA) and toxicity of treatment. RESULTS: One hundred and forty-two patients were followed up until death. The median survival time in the chemotherapy group was 8.7 months (95% confidence interval (CI) 6.9-11.0 months) compared to 6.7 months in the placebo group (95% CI 5.3-7.9 months). Chemotherapy did not affect performance status but slowed the rise of CEA and caused appreciable toxicity. CONCLUSIONS: In this double-blind trial, chemotherapy with 5-fluorouracil plus leucovorin did not improve survival, did not impair performance, but caused appreciable toxicity.