Phase I clinical trial of oral rosiglitazone in combination with intravenous carboplatin in cancer-bearing dogs

Authors

  • S. Allstadt Frazier,

    Corresponding author
    1. Veterinary Medical Teaching Hospital, University of California, Davis, CA, USA
    2. Department of Veterinary Surgical and Radiological Sciences, University of California, Davis, CA, USA
    • Correspondence address:

      S. Allstadt Frazier

      1 Shields Avenue

      2112 Tupper Hall

      Davis

      CA 95616

      USA

      e-mail: sdfrazier@ucdavis.edu

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  • D. S. McKemie,

    1. Department of Molecular Biosciences, University of California, Davis, CA, USA
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  • T. A. Guerrero,

    1. Department of Veterinary Surgical and Radiological Sciences, University of California, Davis, CA, USA
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  • H. LaChapelle,

    1. Veterinary Medical Teaching Hospital, University of California, Davis, CA, USA
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    • Present address: Pebble-Maryland Animal Hospital, Las Vegas, NV 89123, USA

  • K. A. Skorupski,

    1. Veterinary Medical Teaching Hospital, University of California, Davis, CA, USA
    2. Department of Veterinary Surgical and Radiological Sciences, University of California, Davis, CA, USA
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  • P. H. Kass,

    1. Department of Population, Health & Reproduction, University of California, Davis, CA, USA
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  • C. O. Rodriguez Jr

    1. Veterinary Medical Teaching Hospital, University of California, Davis, CA, USA
    2. Department of Veterinary Surgical and Radiological Sciences, University of California, Davis, CA, USA
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  • A portion of this work was presented at the 2011 American College of Veterinary Internal Medicine Forum, Denver, CO, 15–18 June 2011.

Abstract

Rosiglitazone is an FDA-approved peroxisome proliferator-activated receptor gamma (PPARγ) agonist and antidiabetic agent in humans that has been investigated for its ability to reduce tumor cell growth. The purpose of this study was to determine the maximally tolerated dose, peak plasma concentrations and side effect profile of oral rosiglitazone when combined with carboplatin in dogs with cancer. Rosiglitazone was administered at 6 and 8 mg/m2 to seven dogs. Carboplatin was administered at 240–300 mg/m2 in combination with rosiglitazone. For toxicity evaluation, the toxicity data for the seven dogs in this study were combined with the toxicity data from three dogs previously reported in a methodology study. Peak plasma rosiglitazone concentrations varied with dose. The dose-limiting toxicity was hepatic at a dose of 8 mg/m2. Three dogs had mild to moderate alanine aminotransferase elevations but no changes in total bilirubin, alkaline phosphatase, blood glucose or γ-glutamyltranspeptidase values were noted.

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