Prospective evaluation of toceranib phosphate in metastatic canine osteosarcoma.

Abstract

Efficacious therapies for measurable metastatic canine osteosarcoma (OSA) are generally lacking. Preliminary retrospective studies suggested that approximately 50% of dogs with measurable metastatic OSA experienced clinical benefit (objective response or clinically meaningful disease stabilisation) following toceranib (TOC) treatment. The purpose of this clinical trial was to prospectively evaluate the clinical outcome following TOC treatment in dogs with measurable pulmonary metastatic OSA. A secondary goal was to identify potential biomarkers of clinical benefit by measuring changes in plasma vascular endothelial growth factor (VEGF) and circulating regulatory T-cell (Treg) percentage. Twenty-two dogs with pulmonary metastasis from appendicular OSA having undergone previous amputation were treated prospectively with TOC. Adverse events (AEs) were common but predominantly low grade. Nine patients were withdrawn from the study prior to the week 8 assessment of response either due to progressive disease (PD), decreased quality of life or owner perceived unacceptable AEs. Of the patients evaluable for disease progression at week 8 (or earlier), 3/17 (17.6 %) had stable disease with the remainder having PD. The median progression-free survival time for all patients was 57 days (range 7-176 days) with a median overall survival time of 89 days (range 7-574 days). Plasma VEGF concentrations were significantly elevated in patients after 4 weeks of TOC treatment, but no changes were observed in percentage of Treg in peripheral blood. Overall, the results of this clinical trial do not support the use of TOC as single agent therapy for canine metastatic OSA.

• Authors: T Laver, C A London, D M Vail, B J Biller, J Coy, D H Thamm
• Journal: Veterinary and comparative oncology (Vet Comp Oncol) Vol. 16 Issue 1 Pg. E23-E29 (Mar 2018) ISSN: 1476-5829 [Electronic] England
• PMID: 28621057 (Publication Type: Journal Article)
• Copyright: © 2017 John Wiley & Sons Ltd.

Chemical References

• Antineoplastic Agents
• Biomarkers
• Indoles
• Pyrroles
• Vascular Endothelial Growth Factor A
• toceranib phosphate

Topics

• Animals
• Antineoplastic Agents (therapeutic use)
• Biomarkers (blood)
• Bone Neoplasms (drug therapy, mortality, veterinary)
• Dog Diseases (drug therapy, mortality)
• Dogs
• Enzyme-Linked Immunosorbent Assay (veterinary)
• Female
• Indoles (therapeutic use)
• Male
• Osteosarcoma (drug therapy, mortality, veterinary)
• Prospective Studies
• Pyrroles (therapeutic use)
• Survival Analysis
• T-Lymphocytes, Regulatory (drug effects)
• Vascular Endothelial Growth Factor A (blood)