Clinical development of eniluracil/fluorouracil: an oral treatment for patients with solid tumors.
Eniluracil (776C85, GW776) inactivates dihydropyrimidine dehydrogenase (DPD), the principal enzyme of 5-fluorouracil (5-FU) catabolism. Inactivation of DPD eliminates a potential mechanism for tumor 5-FU resistance and permits achievement of reliable and predictable pharmacokinetics following oral 5-FU administration. Eniluracil/5-FU has demonstrated efficacy as monotherapy in patients with a variety of solid tumors when given on a 5 or 28-day dosing schedule. The primary and dose-limiting toxicity is myelosuppression with the 5-day schedule and diarrhea with the 28-day schedule. The frequency of hand-foot syndrome is minimal with either schedule. Phase III pivotal registration-directed studies with eniluracil/5-FU given by the 28-day schedule are ongoing or planned for the near future in patients with advanced colorectal, breast and pancreatic cancer.
Levin
J
J
Glaxo Wellcome, Inc., Research Triangle Park, NC 27709, USA.
Hohneker
J
J
D000284:Administration, Oral; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D014498:Uracil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
D000964:Antimetabolites, Antineoplastic; D004791:Enzyme Inhibitors; C073482:eniluracil; D014498:Uracil; D005472:Fluorouracil