URACIL-TEGAFUR IN GASTRIC-CARCINOMA - A COMPREHENSIVE REVIEW

Purpose: The second-generation oral anticancer agent UFT, a combinatio n of uracil and tegafur (TGF), results in a higher fluorouracil (5-FU) concentration in the tumor tissues than is achieved by TGF or compara ble doses of intravenous 5-fluorouracil. UFT has been extensively stud ied in Japan and has been in use in the Orient for many years, particu larly for patients with gastric carcinoma. UFT has recently entered ex tensive investigations in North America and Europe. Methods: Relevant studies that have chronicled the establishment of UFT, its mechanism o f action, preclinical toxicology, human pharmacokinetics, phase I stud ies, and activity against gastric carcinoma are described in detail. R esults: The uracil in UFT slows degradation of 5-FU by dihydropyrimidi ne dehydrogenase (DPD), which results in sustained concentrations of 5 -FU in blood and tumor tissues, UFT is well tolerated, but such toxic effects as nausea, vomiting, and diarrhea are dose- and schedule-depen dent. In phase I pharmacokinetic studies, UFT given orally on a 28-day schedule resulted in blood concentrations comparable to those followi ng low-dose continuous intravenous infusion of 5-FU. In patients with gastric carcinoma, UFT alone has a response rate of approximately 20%. In the adjuvant setting, UFT plus mitomycin appears superior to TOF p lus mitomycin. In Japan, UFT is part of the standard adjuvant chemothe rapy for gastric carcinoma, Conclusion: UFT is one of the first second -generation oral 5-FU prodrugs under investigation in North America an d Europe. The literature suggests UFT is well tolerated and has cellul ar pharmacokinetic superiority over the first-generation 5-FU prodrug TGF. UFT has a more favorable toxicity profile than intravenous 5-FU, The issues of efficacy, patient convenience, and quality of life need to be studied in controlled randomized trials. J Clin Oncol 16:2877-28 85, (C) 1998 by American Society of Clinical Oncology.