A PROSPECTIVE RANDOMIZED STUDY COMPARING HIGH-DOSE AND LOW-DOSE LEUCOVORIN COMBINED WITH SAME-DOSE 5-FLUOROURACIL IN ADVANCED COLORECTAL-CANCER

Although the efficacy of 5-fluorouracil (5-FU) modulated by leucovorin is well established for advanced colorectal cancer, the question of t he most effective regimen and optimal dose of leucovorin remains unans wered. This prospective randomized trial compares low-dose (group 1) a nd high-dose (group 2) leucovorin, combined with the same dose of 5-FU to determine whether high-dose leucovorin was more beneficial than lo w-dose on overall survival. Inclusion criteria were: unresectable meta static colorectal carcinoma, with or without evaluable tumor response; a performance status of less than grade 3 (World Health Organization classification); and no previous chemotherapy for metastases. Forty-tw o patients were randomized in group 1 (leucovorin, 20 mg/m(2)/day, day s 1 through 5) and 41 patients in group 2 (leucovorin, 200 mg/m(2)/day , days 1-5). All the patients in the two groups received a 1-hour infu sion of 400 mg/m(2)/day 5-FU every 4 weeks. The two groups were matche d with no statistically significant differences in gender ratio, site of primary tumor, performance status, and tumor extent. Toxicity in th e two regimens was low and not significantly different between the two groups. Overall median survival was 346 days in group 1 and 323 days in group 2 and was not significantly different between the two groups. At 1 year, the test of equivalence was significant (p < 0.01), demons trating an absence of more than 20% benefit in 1-year survival for the high-dose regimen. The use of high-dose leucovorin combined with 5-FU in the 5-day regimen does not significantly improve overall survival for patients who have metastatic colorectal cancer.