Cardiovascular Effects of Androgen Deprivation Therapy in Prostate Cancer.

PURPOSE OF THE REVIEW: This review paper is a comprehensive look at the cardiovascular disease (CVD) risk that is associated with the use of androgen deprivation therapy in prostate cancer. It summarizes when certain cancer therapies are indicated and should guide physicians in identifying patients at increased risk for CVD during prostate cancer therapy. RECENT FINDINGS: GnRH agonist use and maximal androgen blockade (MAB) are associated with increased CVD. This association is not observed in patients on GnRH antagonists. One example is the novel agent abiraterone, which is associated with hypertension whose mechanisms are likely driven by mineralocorticoid excess. Incidence of cardiovascular disease events is greatest when using MAB, especially in patients with pre-existing CVD. There is significant confounding that exists given patients with more aggressive cancers tend to be older and have more co-existing CVD. Given the lower CVD event rates with GnRH antagonists, future studies and strategies should focus on high-risk cancer patients with co-existing CVD receiving antagonists over agonists.

Tyrosine Kinase Inhibitor-Induced Hypertension.

PURPOSE OF REVIEW: The purpose of this paper is to identify commonly used tyrosine kinase inhibitors (TKIs) that are associated with hypertension, primarily, vascular endothelial growth factor (VEGF) signaling pathway (VSP) inhibitors. We review the incidence, mechanism, and strategies for management of TKI-induced HTN. We hope to provide clinicians with guidance on how to manage similar clinical scenarios. RECENT FINDINGS: Many of the newer VSP inhibitors are reviewed here, including cediranib, axitinib, pazopanib, and ponatinib. Trials utilizing prophylactic treatment with angiotensin system inhibitors (ASIs) are discussed as well as recent data showing an improvement in overall survival and progression-free survival in patients on ASIs and TKI-induced hypertension. The incidence of TKI-induced HTN among the VEGF inhibitors ranges from 5 to 80% and is dose dependent. Newer generation small-molecule TKIs has a lower incidence. The mechanism of action involves VSP inhibition, leading to decreased nitric oxide and increased endothelin production, which causes vasoconstriction, capillary rarefaction, and hypertension. ASIs and calcium channel blockers are first-line therapy for treatment and are associated with improved overall survival. Nitrates and beta-blockers are associated with in vitro cancer regression; however, there is a paucity of trials regarding their use as an anti-hypertensive agent in the TKI-induced HTN patient population.