Phase I and pharmacokinetic evaluation of floxuridine/leucovorin given on the Roswell Park weekly regimen |
| |
| Authors: | Patrick J. Creaven Youcef M. Rustum Nicholas J. Petrelli Neal J. Meropol Derek Raghavan Miguel Rodriguez-Bigas Ellis G. Levine Cheryl Frank Szilvia Udvary-Nagy April Proefrock |
| |
| Affiliation: | (1) Division of Solid Tumor Oncology and Investigational Therapeutics, Department of Medicine, Roswell Park Cancer Institute, 14263 Buffalo, NY, USA;(2) Division of Experimental Therapeutics and Grace Cancer Drug Center, Roswell Park Cancer Institute, 14263 Buffalo, NY, USA;(3) Department of Surgical Oncology, Roswell Park Cancer Institute, 14263 Buffalo, NY, USA |
| |
| Abstract: | A phase I and pharmacokinetics study was carried out of floxuridine (FdUrd) modulated by leucovorin (LV) given on the Roswell Park regimen (LV given at 500 mg/m2 by 2-h infusion and FdUrd given by i.v. push at 1 h after the start of LV infusion, treatment being given weekly×6). The dose-limiting toxicity was diarrhea; the MTD and recommended dose for phase II studies was 1,650 mg/m2 per week of FdUrd. The dose-response curve was steep, with 3/3 patients treated at a dose of 1,750 mg/m2 developing grade IV diarrhea. With this schedule there was no significant mucositis. Pharmacokinetic parameters showed very wide interpatient variability. Plasma decay was biphasic with at1/2 of approximately 2 h. Plasma clearance was high (>200 l h–1). No correlation between pharmacokinetic parameters and toxicity could be identified. |
| |
| Keywords: | |
| 本文献已被 SpringerLink 等数据库收录！ |
|
