UFT Plus Oral Leucovorin: A New Oral Treatment for Colorectal Cancer.
UFT is an oral antineoplastic agent that combines the 5-fluorouracil (5-FU) prodrug tegafur with uracil in a 1:4 molar ratio. Uracil is added because it competitively inhibits the degradation of 5-FU, resulting in increased plasma and tumor 5-FU concentrations. Although UFT has been available in Japan since 1984, it has only recently been in clinical development in the United States. Beginning in 1991, phase I/II trials of UFT have been conducted in the United States to establish a maximum tolerated dose, evaluate its pharmacokinetics, and assess its efficacy and safety in advanced colorectal cancer. Pharmacokinetic studies demonstrated that UFT 300 mg/m&sup2;/day administered in divided doses every 8 h for 28 days provides an effective oral method of delivering a prolonged exposure to 5-FU. UFT plus oral leucovorin is well tolerated, with diarrhea as the dose-limiting toxicity. Unlike i.v. administered 5-FU, UFT is not associated with significant myelosuppression, mucositis, hand-foot syndrome, or alopecia, and patients have a decreased risk of toxicity-related hospitalization. In a phase II trial in advanced colorectal cancer, UFT plus oral leucovorin produced an objective response rate of 42%, with survival similar to weekly i.v. 5-FU plus leucovorin. The reduced toxicity, efficacy comparable to i.v. 5-FU, and the convenience and cost savings of an orally administered regimen have potential pharmacoeconomic advantages.
Hoff
PM
Division of Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.
Pazdur
R