Annals of Oncology 4:235-240, 1993
© 1993 European Society for Medical Oncology
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Biochemical modulation of 5-fluorouracil: A randomized comparison of sequential methotrexate, 5-fluorouracil and leucovorin versus sequential 5-fluorouracil and leucovorin in patients with advanced symptomatic colorectal cancer
Department of Oncology, Akademiska sjukhuset, University of Uppsala Uppsala, Sweden
Bengt Glimelius, MD, Department of Oncology, Akademiska sjukhuset, S-751 85 Uppsala, Sweden
BACKGROUND: The optimal chemotherapy for advanced colorectal carcinoma is not known. Two regimens, both based upon biochemical modulation of 5-FU, were compared in a randomized multicenter trial.
PATIENTS AND METHODS: A total of 202 symptomatic patients were randomly allocated to receive either sequential methotrexate, 250 mg/m2, during the first 2 hours and 5-FU, 500 mg/m2, at hours 3 and 23 followed by leucovorin rescue initiated at hour 24 (15 mg x 8) (MFL) or sequential 5-FU 500 mg/m2 followed by leucovorin 60 mg/m2 30–40 minutes later, on days 1 and 2 (FLv). Treatments were repeated every 14 days for eight courses and then every 3 to 4 weeks. Four patients were unevaluable.
RESULTS: The two treatments were equally effective with respect to objective response rates (complete (CR) + partial (PR), MFL 17%, FLv 21%), subjective response rates (symptom relief in the absence of severe adverse effects, 45% vs. 37%), and survival (median 7.5 vs. 9 months). All responses lasted at least 4 months. Overall, toxicity was low and comparable between the groups, but serious toxicity was more common in the MFL group.
CONCLUSIONS: Since FLv is easier to administer and carries less risk for serious toxicity, it should be recommended as a first-line treatment before MFL. On either regimen, about 40% of symptomatic patients can expect palliation, i.e., symptomatic relief without severe adverse effects, for at least 4 months.
biochemical modulation, chemotherapy, colorectal cancer, 5-fluorouracil, subjective response
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