Sorafenib Dose Escalation Is Not Uniformly Associated With Blood Pressure Elevations in Normotensive Patients With Advanced Malignancies
Year: 2014
Type: article
Study design: Clinical Trial
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.
DOI: 10.1038/clpt.2014.63
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
Awards: Experimental Therapeutics: Clinical Trials Network with Phase I Emphasis, Translational Medicine and Cancer Therapy with Vasculature-Targeted Agents, Institute for Clinical and Translational Research (UL1), G2897488819, Wisconsin and New Jersey Alliance in Precision Experimental Therapeutics, Institute for Clinical and Translational Research, G673044640, PAAR-Pharmacogenomics of Anticancer Agents Research Group, Phase I Clinical Trials of Anti-Cancer Agents, The Johns Hopkins Translational Science Team and Consortium for ETCTN Studies, Regional Oncology Research Center
OpenAlex ID: W2078330700