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.
Hohneker
J A
JA
Oncology Clinical Development, Glaxo Wellcome Inc., Research Triangle Park, North Carolina, USA.
D000284:Administration, Oral; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy; D042943:Dihydrouracil Dehydrogenase (NADP); D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D010190:Pancreatic Neoplasms / Q000188:drug therapy; D016896:Treatment Outcome; D014498:Uracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use
D000964:Antimetabolites, Antineoplastic; D004791:Enzyme Inhibitors; C073482:eniluracil; D014498:Uracil; D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil