An Algorithm for the Management of Hypertension in the Setting of Vascular Endothelial Growth Factor Signaling Inhibition

Vascular endothelial growth factor (VEGF) signaling is considered to be one of the key factors involved in tumor-associated angiogenesis. Inhibition of angiogenesis has significantly improved anticancer therapy making it one of the cornerstones of treatment for various solid tumors. Several antiangiogenesis inhibitory compounds (eg, bevacizumab, sunitinib, sorafenib) are now widely used in the treatment of patients with colorectal, non-small-cell lung, advanced renal cell, hepatocellular, and breast cancer. One of the most commonly observed side effects of inhibition of VEGF signaling is hypertension, which is dose-dependent and varies in incidence among the different angiogenesis inhibitor drugs. Poorly controlled hypertension not only can lead to cardiovascular events, renal disease, and stroke, but may also necessitate discontinuation of anticancer therapy, thereby potentially limiting overall clinical benefit. In contrast, hypertension induced by VEGF inhibitors has been shown to represent an important pharmacodynamic biomarker of oncologic response. For the practicing oncologist, knowledge and optimal management of this toxicity is essential. Because of the lack of controlled studies on this topic, no clear recommendations are available. In this article, we review the available preclinical and clinical data on the pathogenesis and management of hypertension resulting from anti-VEGF inhibitor therapy and propose a treatment algorithm that our group has now implemented for daily clinical practice.