New Cancer Tx Raises Blood Pressure

The upside of new cancer therapies that block vascular endothelial growth factor (VEGF) signaling is that these agents have improved the outlook for patients with some cancers and are now used as a first line therapy for some tumors. However the downside is that almost 100% of patients who take VEGF inhibitors (VEGFIs) develop high blood pressure, and a subset develops severe hypertension. That is the finding of a study done at the Institute of Cardiovascular and Medical Sciences, University of Glasgow. A review article on the research was published in the May 2014 issue of the Canadian Journal of Cardiology.

A release from the publisher quotes says senior investigator Rhian M. Touyz, MD, PhD as saying, "Exactly how VEGFIs cause hypertension is unknown. However, what is clear is that inhibition of VEGF in the vasculature directly increases blood pressure because hypertension develops acutely in response to VEGFIs and blood pressure returns to normal once the treatment is stopped.”

The release explains that angiogenesis inhibitors are a new class of cancer drugs that are designed to prevent the formation of new blood vessels, thereby stopping or slowing the growth or spread of tumors. Angiogenesis requires the binding of signaling molecules, such as VEGF, to receptors on the surface of normal endothelial cells. When VEGF and other endothelial growth factors bind to their receptors on endothelial cells, signals within these cells are initiated that promote the growth and survival of new blood vessels, which are necessary for tumor growth. Angiogenesis inhibitors interfere with various steps in this process.

Increased blood pressure has been observed in every trial involving VEGFIs and is the most common cardiovascular complication; it has an associated increased risk of fatal adverse cardiovascular events. According to some studies, VEGFI-induced hypertension is not a side effect of treatment, but rather a mechanism-dependent on-target toxicity. This has led to the concept that hypertension might be indicative of effective VEGF inhibition and a positive antiangiogenic response, and as such could be a biomarker of a favorable outcome from VEGFI treatment. "This further adds to the challenges, because improved cancer responsiveness might thus be associated with potentially greater cardiovascular risk," notes Dr. Touyz.

The exact factors that predispose to VEGFI-induced hypertension still remain to be established, say the investigators. However, risk factors that have been associated with VEGFI-induced hypertension include a previous history of hypertension, combination therapy with more than one anti-VEGFI, over 65 years of age, smoking, and possibly high cholesterol. Body mass index, renal function, race, a family history of hypertension, or cardiovascular disease do not seem to predict development of hypertension with VEGFI treatment.