Open AccessPhase I and Pharmacokinetic Evaluation of the Combination of Orally Administered Docetaxel and Cyclosporin A in Tumor‐Bearing Cats
Author(s) -
McEntee M.C.,
Rassnick K.M.,
Bailey D.B.,
Balkman C.E.,
Flanagan J.L.,
Beaulieu B.B.,
Zgola M.M.,
Lewis L.D.,
Page R.L.
Publication year - 2006
Publication title -
journal of veterinary internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.356
H-Index - 103
eISSN - 1939-1676
pISSN - 0891-6640
DOI - 10.1111/j.1939-1676.2006.tb00753.x
Subject(s) - medicine , pharmacokinetics , cats , docetaxel , pharmacology , adverse effect , premedication , toxicity , oral administration , chemotherapy , anesthesia
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.