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. 2018 Mar;16(1):E23-E29.
doi: 10.1111/vco.12328. Epub 2017 Jun 15.

Prospective evaluation of toceranib phosphate in metastatic canine osteosarcoma

Affiliations

Prospective evaluation of toceranib phosphate in metastatic canine osteosarcoma

T Laver et al. Vet Comp Oncol. 2018 Mar.

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 Nine patients were withdrawn from the study prior to the week 8 assessment of response either due to progressive disease (PD), decreased quality of life or owner perceived unacceptable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.

Keywords: dog; metastasis; oncology; osteosarcoma; tyrosine kinase.

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Conflict of interest statement

Conflict of interest

Financial support for this study was provided by Zoetis, Inc. DMV, CAL and DHT are or have served as paid consultants for Zoetis.

Figures

FIGURE 1
FIGURE 1
Changes in plasma vascular endothelial growth factor concentrations following toceranib treatment. A, Scatter plot depicting individual and mean +/− SEM plasma VEGF concentrations for 18 dogs prior to and 28 days following toceranib initiation. B, Individual mean (+/− SEM) pre- and post-toceranib values. Arrows indicate dogs experiencing stable disease at the 8-week recheck.
FIGURE 2
FIGURE 2
Changes in regulatory T-cell percentage following toceranib treatment. A, Scatter plot depicting individual and mean +/− SEM Treg number for 18 dogs prior to and 28 days following toceranib initiation. B, Individual mean (+/− SEM) pre- and post-toceranib values. Arrows indicate dogs experiencing stable disease at the 8-week recheck.
FIGURE 3
FIGURE 3
Kaplan-Meier curves showing progression-free and overall survival time from the time of initiation of treatment for metastatic osteosarcoma with toceranib. The median progression-free survival time was 57 days and the median overall survival time was 89 days.

References

    1. Ehrhart NP, Ryan SD, Fan TM. Tumors of the skeletal system In: Withrow SJ, Vail DM, Page RL, eds. Withrow & MacEwen’s Small Animal Clinical Oncology. 5th ed. St. Louis, MO: Elsevier; 2013:463–503.
    1. Bergman PJ, MacEwen EG, Kurzman ID, et al. Amputation and carboplatin for treatment of dogs with osteosarcoma: 48 cases (1991 to 1993). J Vet Intern Med. 1996;10(2):76–81. - PubMed
    1. Selmic LE, Burton JH, Thamm DH, Withrow SJ, Lana SE. Comparison of carboplatin and doxorubicin-based chemotherapy protocols in 470 dogs after amputation for treatment of appendicular osteosarcoma. J Vet Intern Med. 2014;28(2):554–563. - PMC - PubMed
    1. Skorupski KA, Uhl JM, Szivek A, Allstadt Frazier SD, Rebhun RB, Rodriguez CO Jr. Carboplatin versus alternating carboplatin and doxorubicin for the adjuvant treatment of canine appendicular osteosarcoma: a randomized, phase III trial. Vet Comp Oncol. 2016;14(1):81–87. - PMC - PubMed
    1. Saam DE, Liptak JM, Stalker MJ, Chun R. Predictors of outcome in dogs treated with adjuvant carboplatin for appendicular osteosarcoma: 65 cases (1996-2006). J Am Vet Med Assoc. 2011;238(2):195–206. - PubMed

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