Sorafenib therapy induced a significant increase in mean systolic blood pressure (+10.8 mm Hg; 95% CI, 8.6-13.0; P < 0.0001) that was detectable within the first 24 hours of treatment.
Cohort (n=54)
No
Does ambulatory blood pressure monitoring detect early sorafenib-induced blood pressure elevations in normotensive advanced cancer patients?
Ambulatory blood pressure monitoring can detect significant sorafenib-induced blood pressure elevations within the first 24 hours of treatment, serving as an early pharmacodynamic biomarker of VEGF inhibition.
Estimación del efecto: mean increase 10.8 mm Hg (95% CI 8.6-13.0)
valor p: p=< 0.0001
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.
Maitland et al. (Tue,) conducted a cohort in normotensive advanced cancer (n=54). Sorafenib vs. Baseline (before therapy) was evaluated on Change in mean systolic blood pressure between days 6 and 10 (mean increase 10.8 mm Hg, 95% CI 8.6-13.0, p=< 0.0001). Sorafenib therapy induced a significant increase in mean systolic blood pressure (+10.8 mm Hg; 95% CI, 8.6-13.0; P < 0.0001) that was detectable within the first 24 hours of treatment.