This study was presented as an abstract at the 21st ECVIM-CA 2011 in Seville and the 57th DVG-Vet-Congress 2011 in Berlin
Use of Epothilone B (Patupilone) in Refractory Lymphoma and Advanced Solid Tumors in Dogs
Article first published online: 3 DEC 2012
Copyright © 2012 by the American College of Veterinary Internal Medicine
Journal of Veterinary Internal Medicine
Volume 27, Issue 1, pages 120–125, January/February 2013
How to Cite
Meier, V., Geigy, C., Grosse, N., McSheehy, P. and Rohrer Bley, C. (2013), Use of Epothilone B (Patupilone) in Refractory Lymphoma and Advanced Solid Tumors in Dogs. Journal of Veterinary Internal Medicine, 27: 120–125. doi: 10.1111/jvim.12019
Conflict of Interest: Authors disclose no conflict of interest.
- Issue published online: 11 JAN 2013
- Article first published online: 3 DEC 2012
- Manuscript Accepted: 16 OCT 2012
- Manuscript Revised: 18 SEP 2012
- Manuscript Received: 14 FEB 2012
- Microtubule-stabilizing agents
The epothilones are microtubule-stabilizing agents with promising antitumor effect in refractory and metastatic tumors in humans. The toxicity profile is considered more favorable than in taxanes. The safety of epothilone B (patupilone) has not been evaluated in tumor-bearing dogs.
To evaluate the inhibition of proliferation in canine tumor cells after patupilone treatment. To assess toxicity profile and maximally tolerated dose of patupilone in dogs with refractory tumors.
Twenty client-owned dogs with various malignancies.
Prospective clinical study. The inhibition of proliferation was assessed with a proliferation assay in vitro in canine hemangiosarcoma and lymphoma cell lines. Dogs received patupilone IV once a week for 2 treatments (= 1 treatment cycle). Dose was escalated with 3 dogs per cohort and 20% increments. Adverse effects were graded accor-ding to the VCOG-CTCAE v1.0.
Both canine cell lines were sensitive to patupilone with approximately 50% decrease in proliferative activity at 0.2–1 nM. In vivo, dose-limiting adverse effects occurred at 3.3 mg/m2; main adverse effects were diarrhea, anorexia, vomiting, and nausea. Neither neutropenia nor peripheral neuropathy was observed. Maximally tolerated dose for 2 patupilone administrations once weekly IV is 2.76 mg/m2. Three per 11 dogs receiving more than 1 treatment cycle showed partial remission in the short period of observation.
Conclusions and Clinical Importance
Canine tumor cells show inhibition of proliferation to patupilone in vitro. Clinically, a dose of 2.76 mg/m2 IV is well tolerated in dogs with spontaneously occurring tumors.