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Published on: March 18, 2014
Prospective evaluation of toceranib phosphate in metastatic canine osteosarcoma
T Laver1, C A London2, D M Vail3
1Flint Animal Cancer Center, Colorado State University, Fort Collins, Colorado.
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 Nine patients were withdrawn from the study prior to the week 8 assessment of response either due to progressive disease (PD), decreased quality of life or owner perceived unacceptable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.
Insights
Toceranib (TOC) did not show significant clinical benefit for dogs with metastatic osteosarcoma (OSA). This study found TOC ineffective as a single agent therapy for canine OSA, despite some preliminary positive findings.
Area of Science:
- Veterinary Oncology
- Canine Cancer Research
- Pharmacological Studies in Animals
Background:
- Efficacious treatments for measurable metastatic canine osteosarcoma (OSA) are limited.
- Previous studies suggested potential clinical benefit from toceranib (TOC) in approximately 50% of dogs with metastatic OSA.
Purpose of the Study:
- To prospectively evaluate the clinical outcome of toceranib (TOC) treatment in dogs with measurable pulmonary metastatic OSA.
- To identify potential biomarkers, including plasma vascular endothelial growth factor (VEGF) and circulating regulatory T-cell (Treg) percentage, associated with clinical benefit.
Main Methods:
- A prospective clinical trial involving 22 dogs with pulmonary metastasis from appendicular OSA previously treated with amputation.
- Dogs received prospective treatment with TOC, with adverse events (AEs) and clinical outcomes monitored.
- Plasma VEGF and Treg percentages were measured to assess potential biomarker correlations.
Main Results:
- Nine patients were withdrawn before week 8 due to progressive disease, decreased quality of life, or unacceptable AEs.
- Of the 17 evaluable patients, only 3 (17.6%) had stable disease at week 8; the rest had progressive disease (PD).
- Median progression-free survival was 57 days, and median overall survival was 89 days. Plasma VEGF levels increased, but Treg percentages remained unchanged.
Conclusions:
- The results do not support the use of toceranib (TOC) as a single-agent therapy for canine metastatic osteosarcoma (OSA).
- Further research is needed to explore alternative therapeutic strategies for this challenging condition.
