title: Phase I clinical trial of oral rosiglitazone in combination with intravenous carboplatin in cancer-bearing dogs.
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/m(2) to seven dogs. Carboplatin was administered at 240-300 mg/m(2) 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/m(2). 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.
authors.affiliation: Veterinary Medical Teaching Hospital, University of California, Davis, CA, USA; Department of Veterinary Surgical and Radiological Sciences, University of California, Davis, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Allstadt Frazier
authors.forename: D S
authors.initials: DS
authors.lastname: McKemie
authors.forename: T A
authors.initials: TA
authors.lastname: Guerrero
authors.forename: H
authors.initials: H
authors.lastname: LaChapelle
authors.forename: K A
authors.initials: KA
authors.lastname: Skorupski
authors.forename: P H
authors.initials: PH
authors.lastname: Kass
authors.forename: C O
authors.initials: CO
authors.lastname: Rodriguez
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007275:Injections, Intravenous; D008297:Male; D009369:Neoplasms / Q000188:drug therapy / Q000662:veterinary*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D016190:Carboplatin