PHASE-I AND PHARMACOKINETIC EVALUATION OF FLOXURIDINE/LEUCOVORIN GIVEN ON THE ROSWELL-PARK WEEKLY REGIMEN

A phase T and pharmacokinetics study was carried out of floxuridine (FdUrd) modulated by leucovorin (LV) given on the Roswell Park regimen (LV given at 500 mg/m(2) by 2-h infusion and FdUrd given by i. v. push at 1 h after the start of LV infusion, treatment being given weekly x 6). The dose-limiting toxicity was diarrhea; the MTD and recommended dose for phase II studies was 1,650 mg/m(2) per week of FdUrd. The dose-response curve was steep, with 3/3 patients treated at a dose of 1,750 mg/ m(2) developing grade IV diarrhea. With this schedule there was no significant mucositis. Pharmacokinetic parameters showed very wide interpatient variability. Plasma decay was biphasic with a t(1/2)beta of approximately 2 h. Plasma clearance was high (> 200 1 h(-1)). No correlation between pharmacokinetic parameters and toxicity could be identified.