Sorafenib dose escalation is not uniformly associated with blood pressure elevations in normotensive patients with advanced malignancies.

ABSTRACT: Hypertension after treatment with vascular endothelial growth factor (VEGF) receptor inhibitors is associated with superior treatment outcomes for advanced cancer patients. To determine whether increased sorafenib doses cause incremental increases in blood pressure (BP), we measured 12-h ambulatory BP in 41 normotensive advanced solid tumor patients in a randomized dose-escalation study. After 7 days' treatment (400?mg b.i.d.), mean diastolic BP (DBP) increased in both study groups. After dose escalation, group A (400?mg t.i.d.) had marginally significant further increase in 12-h mean DBP (P = 0.053), but group B (600?mg b.i.d.) did not achieve statistically significant increases (P = 0.25). Within groups, individuals varied in BP response to sorafenib dose escalation, but these differences did not correlate with changes in steady-state plasma sorafenib concentrations. These findings in normotensive patients suggest BP is a complex pharmacodynamic biomarker of VEGF inhibition. Patients have intrinsic differences in sensitivity to sorafenib's BP-elevating effects.

SUBMITTER: Karovic S 

PROVIDER: S-EPMC4165641 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature