Angiogenesis Inhibitors and Hypertension: Clinical Aspects

Inhibition of angiogenesis with antibodies against vascular endothelial growth
factor (VEGF) or VEGF receptor antagonists (tyrosine kinase inhibitors) has
become an established treatment for cancer. An unanticipated side effect of
angiogenesis inhibitors is the development of hypertension.
The pathogenesis of this hypertension is unknown. Not all patients will develop
hypertension. However, it is not known which patient will and which patient
will not develop hypertension.

The aim of the study is:
- To find simple clinical and/or laboratory parameters to predict the
development of hypertension during treatment with the tyrosine kinase inhibitor
Sunitinib. If such parameters are present it will be evaluated prospectively
whether one or more of these parameters predict the development of hypertension
in a second cohort of patients treated with Sunitinib.
- To elucidate the mechanism of hypertension during treatment with the tyrosine
kinase inhibitor Sunitinib and therefore providing more insight in the
pathogenesis of essential hypertension in the overall population.

This is a single centre, prospective, observational study. In total 80 patients
intended to be treated with Sunitinib will be included. They will be asked to
complete a questionnaire. During the follow-up of 10 weeks, at baseline, 4 and
10 weeks after starting treatment with Sunitinib, blood and urine samples will
be collected and non-ambulatory and ambulatory blood pressure measurement will
be performed. Blood pressure will be classified according to the WHO criteria
for hypertension in stage 0, stage I, stage II and stage III. Demographic and
laboratory parameters of the groups of patients either developing an increase
in blood pressure or not will be compared. If such parameters are present it
will prospectively be evaluated whether one or more of these parameters predict
the development of hypertension in a second cohort of patients treated with an
angiogenesis inhibitor.

The risks associated with participation are almost similar as to no
participation and include the risks associated with the treatment with
Sunitinib. In addition, the standard risks associated with the use of an
intravenous canula must be mentioned. The 24-hour ambulatory blood pressure
measurement might be considered as a burden. Non-ambulatory blood pressure
measurement requires a 30 minute stay in the hospital during a routine visit at
the outpatient clinic.