Phase I and Pharmacokinetic Trial of Weekly Oral Fluorouracil Given With Eniluracil and Low-Dose Leucovorin to Patients With Solid Tumors

摘要: PURPOSE: Fluorouracil (5-FU) given as a weekly, high-dose 24-hour infusion is active and tolerable. We evaluated an oral regimen of eniluracil (which inactivates dihydropyrimidine dehydrogenase [DPD]), 5-FU, leucovorin to simulate this schedule. PATIENTS AND METHODS: Patients received single 5-FU (2,300 mg/m2 on day 2) with (15 mg orally [PO] bid days 1 through 3) provide reference pharmacokinetic data. Two weeks later, patients began treatment (20 mg) (PO (10 15 PO 2). RESULTS: Dose-limiting toxicity (diarrhea, neutropenia, fatigue) was seen 2 weekly for either 6 8 or 3 4 weeks, whereas five seven tolerated 10 weeks. Eniluracil led 35-fold reduction in clearance. Fluoro-beta-alanine, catabolite, not detected plasma during 5-FU–enilurac...