Hypertension and Rarefaction during Treatment with Telatinib, a Small Molecule Angiogenesis Inhibitor
Why the study?
Does telatinib impair vascular function, induce rarefaction, and cause hypertension in patients with advanced solid tumors?
Population
Patients with advanced solid tumors
Comparison
Telatinib for 5 weeks vs Baseline measurements (pre-treatment)
Design
Cohort
Follow-up
5 weeks
Authors
Discussion
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Implication
May warrant BP and vascular monitoring with telatinib; supports antiangiogenic TKI toxicity hypothesis but leaves open causality and outcomes.
Key Points
- To investigate whether telatinib, an antiangiogenic small molecule tyrosine kinase inhibitor, impairs vascular function, induces microvascular rarefaction, and causes hypertension.
- Conducted a side-study within a phase I clinical trial of telatinib in patients with advanced solid tumors.
- Evaluated blood pressure, flow-mediated dilation, nitroglycerin-mediated dilation, aortic pulse wave velocity, laser Doppler skin blood flux, and sidestream dark field capillary density at baseline and after 5 weeks of treatment.
- Systolic and diastolic blood pressure increased significantly by +6.6 mm Hg (P = 0.009) and +4.7 mm Hg (P = 0.016), respectively, while aortic pulse wave velocity increased by 1.2 m/s (P = 0.001).
- Endothelial and smooth muscle function deteriorated, with flow-mediated dilation decreasing by -2.1% (P = 0.003) and nitroglycerin-mediated dilation decreasing by -5.1% (P = 0.001).
- Microvascular density and perfusion fell significantly, with capillary density dropping from 20.8 to 16.7 loops (P = 0.015) alongside reduced skin blood flux (P = 0.015) and incident or worsening proteinuria in six patients.
Structured PICO
Does telatinib impair vascular function, induce rarefaction, and cause hypertension in patients with advanced solid tumors?
P
Population
Patients with advanced solid tumors
I
Intervention
Telatinib (small molecule tyrosine kinase inhibitor of vascular endothelial growth factor receptors 2 and 3, platelet-derived growth factor receptor, and c-KIT) for 5 weeks
C
Comparator
Baseline measurements (pre-treatment)
O
Outcome
Changes in blood pressure, flow-mediated dilation, nitroglycerin-mediated dilation, aortic pulse wave velocity, skin blood flux, and capillary density at 5 weekssurrogate
Treatment with the angiogenesis inhibitor telatinib is associated with increased blood pressure, impaired vascular function, and structural rarefaction.
Cite This Study
Steeghs et al. (2008) studied this question.