Effects of Novel Angiogenesis Inhibitors for the Treatment of Cancer on the Cardiovascular System

Abstract

A 60 year-old man with a history of prostate cancer who underwent radical prostatectomy is currently being treated with androgen-deprivation therapy and is on a clinical trial with bevacizumab (Avastin, an antiangiogenic and anti–vascular endothelia growth factor [VEGF] chemotherapy) for an elevated prostate-specific antigen. At clinic visits after starting bevacizumab, he was noted to have new hypertension, with blood pressure as high as 178/98 mm Hg. After his second cycle of bevacizumab, he had sudden onset of palpitations, with workup revealing atrial fibrillation. He spontaneously cardioverted back to sinus rhythm but was referred to our institution's cardiology clinic for oncology patients (Cardio-Oncology Clinic) for management of hypertension and atrial fibrillation in the setting of bevacizumab therapy. Angiogenesis, the formation of new blood vessels from preexisting ones, is required for the growth and metastases of solid tumors.1 Angiogenesis is mediated by the stabilization of the master transcription factor (hypoxia-inducible factor-α), leading to transcription of a number of protumorigenic factors, including VEGF. Inhibiting this pathway has served as a target for antineoplastic treatment, and over the last 5 years, VEGF signaling pathway (VSP) inhibitors have been approved for the treatment of a broad spectrum of malignancies (the Figure). With increased clinical use, these agents have been shown to have cardiovascular side effects, most commonly hypertension, but also arterial or venous thrombotic events and heart failure. This review outlines the presentation, pathophysiology, and our approach to the diagnosis and treatment of VSP inhibitor–induced hypertension, and briefly highlights other cardiac complications that may occur in patients receiving these agents. Figure. Schematic of vascular endothelial growth factor (VEGF) pathway and sites of action of VEGF signaling pathway inhibitors (modified from templates provided by www.proteinlounge.com). VEGFR indicates VEGF receptor; HIF, hypoxia-inducible factor; PDGF, platelet-derived growth factor; PDGFR, PDGF receptor; and TKI, tyrosine kinase inhibitor. The VEGF …