C21 - Evaluation of Cardiac and Endothelial Dysfunction in Canine Cancer Patients Treated with Toceranib Phosphate

Abstract: Background:
Toceranib phosphate is a tyrosine kinase inhibitor (TKI) and a non-selective inhibitor of Vascular Endothelial Growth Factor (VEGF). While hypertension has been documented as a side effect in canine patients receiving TKIs, to date, there have not been studies evaluating left ventricular systolic function and endothelial function in canine patients.

Objectives:
To characterize changes in echocardiographic parameters and biomarkers of endothelial function in canine patients treated with toceranib.

Animals:
12 client-owned dogs diagnosed with neoplasia (mast cell tumors N=5, anal sac adenocarcinoma N=4, thyroid carcinoma, mesothelioma, and multiple N=1) receiving single agent toceranib for cancer treatment.

Methods:
This is a prospective study approved by the Tufts University IACUC. Patients had echocardiographic exams and blood pressure measurements. Blood and urine samples were obtained to evaluate levels of VEGF, endothelin-1, platelet derived growth factor (PDGF), prostacyclin, nitric oxide (nitrite and nitrate) metabolites, and cGMP using commercially available ELISA kits. Examination time-points include baseline, one-, three-, and five- months after start of treatment. Statistical analysis was performed using repeated measures mixed models.

Results:
Statistically significant decreases in urine nitrate and plasma prostacyclin concentrations were detected over time. Although not reaching statistical significance, VEGF and systolic blood pressure increased. Four of the study dogs required treatment with hypertension medication (BP > 170mmHg). No significant changes in ejection fraction or fractional shortening were observed.

Conclusions:
Biomarkers of endothelial dysfunction associated with hypertension, including prostacyclin and nitrate, decreased during treatment with toceranib. Larger sample size will be required to confirm the findings of this study.