Investigational New Drugs

, Volume 18, Issue 4, pp 331–342 | Cite as

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

  • Paulo M. Hoff


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.

dihydropyrimidine dehydrogenase fluoropyrimidines leucovorin oral chemotherapy S-1 UFT 


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© Kluwer Academic Publishers 2000

Authors and Affiliations

  • Paulo M. Hoff
    • 1
  1. 1.Department of Gastrointestinal Oncology and Digestive DiseasesThe University of Texas M.D. Anderson Cancer CenterHoustonUSA

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