Evaluation of satraplatin in dogs with spontaneously occurring malignant tumors

Kim A. Selting, X. Wang, D. L. Gustafson, C. J. Henry, J. A. Villamil, D. L. McCaw, D. Tate, M. Beittenmiller, C. Garnett, J. D. Robertson

Research output: Contribution to journalArticlepeer-review


Background: Satraplatin is the 1st orally bioavailable platinum anticancer drug. Objective: Our objectives were to evaluate efficacy in vitro against a canine cancer cell line, to determine the maximally tolerated dose (MTD) of satraplatin in tumor-bearing dogs, to identify the dose-limiting and other toxicities in dogs, and to record pharmacokinetics (PK). Animals: Dogs with macro- or microscopic malignant neoplasia. Methods: D17 canine osteosarcoma cells first were evaluated in a clonogenic survival assay. Then, dogs with a diagnosis of malignant neoplasia were prospectively entered in standard 3 + 3 cohorts. Additional patients were entered at the MTD to assess efficacy. Total and free platinum (by ultrafiltrate) concentrations were determined with inductively coupled plasma mass spectroscopy. Results: Satraplatin inhibited clonogenic survival in vitro at clinically relevant and achievable concentrations. Twenty-three dogs were treated, 14 with PK evaluation. The MTD was 35mg/m 2/d for 5 days, repeated every 3-4 weeks. Bioavailability was 41%. PK variables (mean ± SD) at the MTD included T max 1.8 (± 0.7) hours, C max 72 (± 26)ng/mL, area under concentration (AUC) 0-24 h 316 (± 63)h × ng/mL, and MRT 7 (± 1.3) hours. Higher AUC after the 5th versus the 1st dose suggested drug accumulation. Interestingly, platelets consistently reached nadir sooner than did neutrophils (day 14 versus 19). Myelosuppression was dose-limiting and gastrointestinal toxicity was mild. Conclusions and Clinical Importance: Satraplatin was well tolerated in tumor-bearing dogs, thus warranting further investigation in a phase II trial.

Original languageEnglish (US)
Pages (from-to)909-915
Number of pages7
JournalJournal of veterinary internal medicine
Issue number4
StatePublished - Jul 2011
Externally publishedYes


  • Canine
  • Chemotherapy
  • Clinical pharmacology
  • Pharmacokinetics
  • Pharmacology

ASJC Scopus subject areas

  • General Veterinary


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