Effect of the Vascular Endothelial Growth Factor Inhibitor Toceranib on Cardiac Function and Endothelial Dysfunction Biomarkers in Dogs With Cancer.

BACKGROUND: Hypertension is documented in dogs with cancer receiving toceranib, but no studies have evaluated left ventricular (LV) systolic function and biomarkers of endothelial function. OBJECTIVES: To characterize changes in echocardiographic variables and biomarkers of endothelial function in dogs treated with toceranib. ANIMALS: Twenty-six client-owned dogs with no evidence of pre-existing cardiac disease or systemic hypertension are receiving a single agent toceranib for cancer treatment. METHODS: Dogs were enrolled in this prospective observational study with study visits at baseline, 1, 3, and 5 months after starting toceranib for echocardiographic exams, blood and urine collection, and blood pressure measurements, with an additional blood pressure obtained 2 weeks after starting toceranib. Serum markers of vascular endothelial function (VEGF, endothelin-1, platelet derived growth factor [PDGF], prostacyclin, cyclic guanosine monophosphate [cGMP]) and urinary nitrate were evaluated with ELISA. RESULTS: Dogs were enrolled between 2019 and 2023. Systolic blood pressure increased 2 weeks after initiating toceranib treatment (p = 0.009). Serum prostacyclin concentration was lower after 1 month of treatment (mean 98.8 pg/mL vs. 140.0 pg/mL at baseline, p = 0.03), and serum VEGF concentration was higher after 3 months of treatment (mean of 247.8 pg/mL vs. 135.4 pg/mL at baseline, p = 0.01). Global longitudinal strain (GLS) decreased at the five-month time point (mean -14.5% vs. -15.7% at baseline, p = 0.048) with no significant change in LV fractional shortening by M-mode or ejection fraction by Simpson's method of discs. CONCLUSIONS: Dogs treated with toceranib might have higher systemic blood pressure associated with changes in VEGF and prostacyclin and decreased systolic function.