Vascular endothelial growth factor signaling pathway inhibitors are associated with cardiovascular toxicities including severe hypertension (7.4%), cardiac dysfunction (2.3%), and arterial thromboembolism (1.8%), particularly in patients with preexisting coronary artery disease or hypertension.
Preexisting or coexisting conditions that reduce vascular reserve may increase the risk of cardiotoxicity with VEGF inhibitors, necessitating vigilance and early recognition in cancer patients.
Angiogenesis inhibitors targeting the vascular endothelial growth factor (VEGF) signaling pathway (VSP) have been important additions in the therapy of various cancers, especially renal cell carcinoma and colorectal cancer. Bevazicumab, the first VSP to receive FDA approval in 2004 targeting all circulating isoforms of VEGF-A, has become one of the best-selling drugs of all times. The second wave of tyrosine kinase inhibitors (TKIs), which target the intracellular site of VEGF receptor kinases, began with the approval of sorafenib in 2005 and sunitinib in 2006. Heart failure was subsequently noted, in 2-4% of patients on bevacizumab and in 3-8% of patients on VSP-TKIs. The very fact that the single-targeted monoclonal antibody bevacizumab can induce cardiotoxicity supports a pathomechanistic role for the VSP and the postulate of the "vascular" nature of VSP inhibitor cardiotoxicity. In this review we will outline this scenario in greater detail, reflecting on hypertension and coronary artery disease as risk factors for VSP inhibitor cardiotoxicity, but also similarities with peripartum and diabetic cardiomyopathy. This leads to the concept that any preexisting or coexisting condition that reduces the vascular reserve or utilizes the vascular reserve for compensatory purposes may pose a risk factor for cardiotoxicity with VSP inhibitors. These conditions need to be carefully considered in cancer patients who are to undergo VSP inhibitor therapy. Such vigilance is not to exclude patients from such prognostically extremely important therapy but to understand the continuum and to recognize and react to any cardiotoxicity dynamics early on for superior overall outcomes.
Touyz et al. (Thu,) conducted a review in Cancer. Vascular endothelial growth factor (VEGF) signaling pathway inhibitors was evaluated. Vascular endothelial growth factor signaling pathway inhibitors are associated with cardiovascular toxicities including severe hypertension (7.4%), cardiac dysfunction (2.3%), and arterial thromboembolism (1.8%), particularly in patients with preexisting coronary artery disease or hypertension.