This work was performed at the University of Missouri Veterinary Medical Teaching Hospital, Columbia, MO. Results were presented at the 2009 American College of Veterinary Internal Medicine Forum in Montreal, Quebec, Canada.
Evaluation of Satraplatin in Dogs with Spontaneously Occurring Malignant Tumors
Article first published online: 12 MAY 2011
Copyright © 2011 by the American College of Veterinary Internal Medicine
Journal of Veterinary Internal Medicine
Volume 25, Issue 4, pages 909–915, July/August 2011
How to Cite
Selting, K.A., Wang, X., Gustafson, D.L., Henry, C.J., Villamil, J.A., McCaw, D.L., Tate, D., Beittenmiller, M., Garnett, C. and Robertson, J.D. (2011), Evaluation of Satraplatin in Dogs with Spontaneously Occurring Malignant Tumors. Journal of Veterinary Internal Medicine, 25: 909–915. doi: 10.1111/j.1939-1676.2011.0727.x
- Issue published online: 20 JUL 2011
- Article first published online: 12 MAY 2011
- Submitted November 2, 2010; Revised December 30, 2010; Accepted March 8, 2011.
- Clinical pharmacology;
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 35 mg/m2/d for 5 days, repeated every 3–4 weeks. Bioavailability was 41%. PK variables (mean ± SD) at the MTD included Tmax 1.8 (± 0.7) hours, Cmax 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.