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 o f DPD eliminates a potential mechanism for tumor 5-FU resistance and permit s achievement of reliable and predictable pharmacokinctics following oral 5 -FU administration. Eniluracil/5-FU has demonstrated efficacy as monotherap y in patients with a variety of solid tumors when given on a 5 or 28-day do sing schedule. The primary and dose-limiting toxicity is myelosuppresion wi th 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 re gistration-directed studies with eniluracil/5-FU given by the 28-day schedu le are ongoing or planned for the near future in patients with advanced col orectal, breast and pancreatic cancer.