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


METHODS
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.


CONCLUSIONS
The increase in blood pressure observed in the treatment with telatinib, an angiogenesis inhibitor, may be caused by functional or structural rarefaction.
Department of Clinical Oncology, Leiden University Medical Center, Leiden, the Netherlands. n.steeghs@lumc.nl
Neeltje
N
Steeghs
Hans
H
Gelderblom
Jos Op 't
JO
Roodt
Olaf
O
Christensen
Prabhu
P
Rajagopalan
Marcel
M
Hovens
Hein
H
Putter
Ton J
TJ
Rabelink
Eelco
E
de Koning
D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects* / Q000473:pathology*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000139:chemically induced*; D017078:Laser-Doppler Flowmetry; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D012867:Skin / Q000098:blood supply / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D011505:Protein-Tyrosine Kinases