Phase I and pharmacokinetic evaluation of the combination of orally administered docetaxel and cyclosporin A in tumor-bearing cats.
Intravenously administered docetaxel (DT) is problematic in cats because of the requirement for premedication to ameliorate acute vehicle-induced hypersensitivity reactions. Previously we have revealed that therapeutic plasma concentrations of DT can be achieved in normal and tumor-bearing dogs when DT is administered PO in combination with oral cyclosporin A (CSA). The purpose of this study was to identify the maximally tolerated dosage and characterize the pharmacokinetic disposition of oral DT combined with CSA in cats with tumors. Eighteen tumor-bearing cats were enrolled in this phase I dose escalation and pharmacokinetic study. DT was administered by gavage with CSA (5 mg/kg) twice over a 3-week period. The starting dose of DT was 1.0 mg/kg. Based on the clinical toxicity profile, with gastrointestinal adverse effects and hematologic toxicity the maximal tolerated dose of oral DT was 1.75 mg/kg in combination with 5 mg/kg CSA. Additional studies are necessary to determine the efficacy of DT/CSA in cats with epithelial tumors.
McEntee
M C
MC
College of Veterinary Medicine, Cornell University, Ithaca, NY 14852-6401, USA. mcm43@cornell.edu
Rassnick
K M
KM
Bailey
D B
DB
Balkman
C E
CE
Flanagan
J L
JL
Beaulieu
B B
BB
Zgola
M M
MM
Lewis
L D
LD
Page
R L
RL
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002371:Cat Diseases / Q000188:drug therapy*; D002415:Cats; D016572:Cyclosporine / Q000009:adverse effects / Q000493:pharmacokinetics*; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D008297:Male; D009369:Neoplasms / Q000188:drug therapy / Q000662:veterinary*; D043823:Taxoids / Q000009:adverse effects / Q000493:pharmacokinetics*
D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D016572:Cyclosporine