RT Journal Article
SR Electronic
T1 Ambulatory Monitoring Detects Sorafenib-Induced Blood Pressure Elevations on the First Day of Treatment
JF Clinical Cancer Research
JO Clin Cancer Res
FD American Association for Cancer Research
SP 6250
OP 6257
DO 10.1158/1078-0432.CCR-09-0058
VO 15
IS 19
A1 Maitland, Michael L.
A1 Kasza, Kristen E.
A1 Karrison, Theodore
A1 Moshier, Kristin
A1 Sit, Laura
A1 Black, Henry R.
A1 Undevia, Samir D.
A1 Stadler, Walter M.
A1 Elliott, William J.
A1 Ratain, Mark J.
YR 2009
UL http://clincancerres.aacrjournals.org/content/15/19/6250.abstract
AB Purpose: Hypertension is a mechanism-based toxicity of sorafenib and other cancer therapeutics that inhibit the vascular endothelial growth factor (VEGF) signaling pathway. This prospective, single-center, cohort study characterized ambulatory blood pressure monitoring as an early pharmacodynamic biomarker of VEGF signaling pathway inhibition by sorafenib.Experimental Design: Fifty-four normotensive advanced cancer patients underwent 24-hour ambulatory blood pressure monitoring before and between days 6 and 10 of sorafenib therapy. After blood pressure changes were detected among the first cohort within 10 days, ambulatory blood pressure monitoring was done during the first 24 hours of treatment for the second cohort.Results: For the entire patient population, the blood pressure increase [mean systolic, +10.8 mm Hg; 95% confidence interval (95% CI), 8.6-13.0; range, −5.2 to +28.7 mm Hg; mean diastolic, +8.0 mm Hg; 95% CI, 6.3-9.7; range, −4.4 to +27.1 mm Hg] was detected between days 6 and 10 (P < 0.0001 for both) and plateaued thereafter. Variability in blood pressure change did not associate with: age, body size, sex, self-reported race, baseline blood pressure, or steady-state sorafenib plasma concentrations. In the second cohort, the blood pressure elevation was detected during the first 24 hours (mean systolic, +8.2 mm Hg; 95% CI, 5.0-11.3; mean diastolic, +6.5 mm Hg; 95% CI, 4.7-8.3; P < 0.0001 for both).Conclusions: Ambulatory blood pressure monitoring detects the blood pressure response to VEGF signaling pathway inhibition by sorafenib during the first 24 hours of treatment. The magnitude of blood pressure elevation is highly variable and unpredictable but could be important in optimizing the therapeutic index of VEGF signaling pathway inhibitor therapy. (Clin Cancer Res 2009;15(19):6250–7)