Phase I study of eniluracil,oral 5-fluororacil and gemcitabine in patients with advanced malignancy

Purpose: The objectives of this trial wereto assess the maximal tolerated dose andtoxicity of the combination of oraleniluracil and 5-fluorouracil andintravenous gemcitabine. Patients and methods: Patients withhistologically confirmed, incurablemalignancy (solid tumor or lymphoma)refractory to standard therapy or for whichno standard therapy exists were enrolled. The treatment plan consisted of weeklygemcitabine for three weeks with twicedaily dosing of 5-FU and eniluracil for 21days beginning on day one of gemcitabine. Cycles repeated on an every four weekschedule. The initial cohort receivedgemcitabine 800 mg/m², oral 5-FU 0.6 mg/m²and eniluracil 6.0 mg/m². Results: Twenty-six patients were enrolled. Eight patients received less than 2 cyclesof therapy. Hematologic andgastrointestinal toxicity predominated,with 48% of courses resulted in grade oneor two neutropenia. Hematologic toxicitywas dose limiting. One treatment relateddeath occurred. Conclusions: The combination of eniluracil,5-fluorouracil and gemcitabine offers anoral alternative for 5-FU administration.The recommended phase II dose isgemcitabine 1000 mg/m², 5FU 1.2 mg/m² andeniluracil 12 mg/m².