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...

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Bibliographic Details
Published in:Journal of veterinary internal medicine 2006-11, Vol.20 (6), p.1370-1375
Main Authors: 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
Format: Article
Language:English
Subjects:
Administration, Oral
Animals
antineoplastic agents
Antineoplastic Agents - adverse effects
Antineoplastic Agents - pharmacokinetics
Area Under Curve
Cat Diseases - drug therapy
Cats
Chemotherapy
Clinical trial
clinical trials
combination drug therapy
cyclosporine
Cyclosporine - adverse effects
Cyclosporine - pharmacokinetics
cyclosporins
Docetaxel
dosage
Dose-Response Relationship, Drug
drug evaluation
Drug Therapy, Combination
Female
gavage
Male
maximal tolerated dose
neoplasms
Neoplasms - drug therapy
Neoplasms - veterinary
oral administration
Pharmacokinetics
Taxoids - adverse effects
Taxoids - pharmacokinetics
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Summary: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.
ISSN:0891-6640
1939-1676
DOI:10.1111/j.1939-1676.2006.tb00753.x