Clinical development of eniluracil: current status.

Eniluracil is a potent inactivator of dihydropyrimidine dehydrogenase (DPD), which is the first enzyme in the degradative pathway of systemically administered 5-fluorouracil (5-FU). Two completely oral regimens of eniluracil plus 5-FU are being evaluated in clinical trials: (1) a chronic schedule with both agents administered BID in a 10:1 ratio for 28 days of a 5-week course, and (2) a 5-day schedule of eniluracil once daily on days 1 through 7 and 5-FU once daily on days 2 through 6. The clinical development of eniluracil is being pursued in several tumor types, including colorectal cancer, breast cancer, and pancreatic cancer. Response rates achieved in a phase II study of the chronic schedule of oral eniluracil/5-FU in patients with colorectal cancer compare favorably with those obtained in trials of intravenous 5-FU and leucovorin, while results from other trials are awaited. Safety analysis for the 28-day schedule has revealed a low incidence of severe toxicities, particularly as compared with standard 5-FU regimens.