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/m²/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.