Hypertension and rarefaction during treatment with telatinib, a small molecule angiogenesis inhibitor.

ABSTRACT

PURPOSE: Hypertension is a commonly reported side effect in antiangiogenic therapy. We investigated the hypothesis that telatinib, a small molecule angiogenesis inhibitor, impairs vascular function, induces rarefaction, and causes hypertension. EXPERIMENTAL DESIGN: A side-study was done in a phase I trial of telatinib, a small molecule tyrosine kinase inhibitor of vascular endothelial growth factor receptors 2 and 3, platelet-derived growth factor receptor, and c-KIT in patients with advanced solid tumors. Measurements of blood pressure, flow-mediated dilation, nitroglycerin-mediated dilation, aortic pulse wave velocity, skin blood flux with laser Doppler flow, and capillary density with sidestream dark field imaging were done at baseline and after 5 weeks of treatment. Blood pressure and proteinuria were measured weekly. RESULTS: Mean systolic and diastolic blood pressure values increased significantly at +6.6 mm Hg (P = 0.009) and +4.7 mm Hg (P = 0.016), respectively. Mean flow-mediated dilation and mean nitroglycerin-mediated dilation values significantly decreased by -2.1% (P = 0.003) and -5.1% (P = 0.001), respectively. After 5 weeks of treatment, mean pulse wave velocity significantly increased by 1.2 m/s (P = 0.001). A statistically significant reduction of mean skin blood flux of 532.8% arbitrary units was seen (P = 0.015). Capillary density statistically significantly decreased from 20.8 to 16.7 capillary loops (P = 0.015). Proteinuria developed or increased in six patients during telatinib treatment. CONCLUSION: The increase in blood pressure observed in the treatment with telatinib, an angiogenesis inhibitor, may be caused by functional or structural rarefaction.