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Hypertension and Rarefaction during Treatment with Telatinib, a Small Molecule Angiogenesis Inhibitor

Hypertension and Rarefaction during Treatment with Telatinib, a Small Molecule Angiogenesis... 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. rarefaction hypertension vascular endothelial growth factor tyrosine kinase inhibitor angiogenesis inhibitor telatinib http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Clinical Cancer Research American Association of Cancer Research

Hypertension and Rarefaction during Treatment with Telatinib, a Small Molecule Angiogenesis Inhibitor

Hypertension and Rarefaction during Treatment with Telatinib, a Small Molecule Angiogenesis Inhibitor

Clinical Cancer Research , Volume 14 (11): 3470 – Jun 1, 2008

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. rarefaction hypertension vascular endothelial growth factor tyrosine kinase inhibitor angiogenesis inhibitor telatinib

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References (42)

Publisher
American Association of Cancer Research
Copyright
Copyright © 2010 American Association for Cancer Research
ISSN
1078-0432
eISSN
1557-3265
DOI
10.1158/1078-0432.CCR-07-5050
pmid
18519779
Publisher site
See Article on Publisher Site

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. rarefaction hypertension vascular endothelial growth factor tyrosine kinase inhibitor angiogenesis inhibitor telatinib

Journal

Clinical Cancer ResearchAmerican Association of Cancer Research

Published: Jun 1, 2008

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