Phase I Assessment of the Pharmacokinetics, Metabolism, and Safety of Emitefur in Patients With Refractory Solid Tumors

PURPOSE: To determine the toxicities, dose-limiting toxicities (DLT), maximum-tolerated dose, and pharmacokinetic profile of emitefur (BOF-A2) in patients with advanced solid tumors. METHODS: This was a phase I dose-escalating trial in which cohorts of patients received BOF-A2 (cohort 1, 300 mg/m2 orally [PO] tid; cohort 2, 200 mg/m2 PO tid; cohort 3, 200 mg/m2 bid; and cohort 4, 250 mg/m2 bid) for 14 consecutive days followed by 1 week of rest (cycle 1). Pharmacokinetics, toxicity, and tumor response were monitored. RESULTS: Nineteen patients received 110 cycles (three patients in cohort 1, three patients in cohort 2, 10 patients in cohort 3, and three patients in cohort 4). DLT (grade 3 stomatitis, diarrhea, leukopenia) was observed in cohorts 1, 2, and 4. Pharmacokinetics indicated that prolonged systemic expression of fluorouracil (5-FU) is maintained after administration of BOF-A2 at a dose of 200 mg bid for 14 days. The mean steady-state concentration of plasma 5-FU was ≥ 24 ng/mL, which was 184-fol...