Phase I and pharmacokinetic evaluation of floxuridine/leucovorin given on the Roswell Park weekly regimen.
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 x 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 a t1/2 beta of approximately 2 h. Plasma clearance was high (> 200 1 h-1). No correlation between pharmacokinetic parameters and toxicity could be identified.
Creaven
P J
PJ
Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263.
Rustum
Y M
YM
Petrelli
N J
NJ
Meropol
N J
NJ
Raghavan
D
D
Rodriguez-Bigas
M
M
Levine
E G
EG
Frank
C
C
Udvary-Nagy
S
S
Proefrock
A
A
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome
D005467:Floxuridine; D002955:Leucovorin