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The Tegafur-Based Dihydropyrimidine Dehydrogenase Inhibitory Fluoropyrimidines, UFT/Leucovorin (ORZEL and S-1: a Review of Their Clinical Development and Therapeutic Potential

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Abstract

Protracted intravenous regimens of fluorouracil (5-FU) may besuperior and better tolerated than intravenous bolus dosing. Aneffective oral regimen would allow a protracted course of 5-FUwithout the need for central venous lines and the associatedincrease in complications. Approximately 85% of 5-FU is degradedby dihydropyrimidine dehydrogenase (DPD); inhibition of thisenzyme pathway can increase the amount of circulating 5-FU. Two oralfluoropyrimidines commonly referred to as DPD inhibitoryfluoropyrimidines, or DIFs, UFT® plus leucovorin(LV) and S-1 are reviewed herein. These agents represent anapproach to more convenient, less toxic 5-FU therapy. In twomulticenter, randomized, phase III trials in patients withadvanced colorectal cancer, UFT/LV produced equivalent activitycompared with intravenous 5-FU/LV but with significantly lessmajor toxicity. The predominant side effect of UFT, diarrhea, isgenerally self-limited and easily managed. Myelosuppression andhand-foot syndrome were rarely noted in the schedules used inthese trials. S-1 has demonstrated promising activity in phaseII trials conducted in patients with gastric, colorectal, breast,and head and neck cancers. Ongoing trials are defining the rolesof these agents in a variety of malignancies.

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Hoff, P.M. The Tegafur-Based Dihydropyrimidine Dehydrogenase Inhibitory Fluoropyrimidines, UFT/Leucovorin (ORZEL and S-1: a Review of Their Clinical Development and Therapeutic Potential. Invest New Drugs 18, 331–342 (2000). https://doi.org/10.1023/A:1006445214741

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