Aortic Dissection and Cardiac Dysfunction Emerged Coincidentally During the Long-Term Treatment with Angiogenesis Inhibitors for Metastatic Renal Cell Carcinoma

Abstract

Angiogenesis inhibitors, such as sorafenib and axitinib, which target vascular endothelial growth factor (VEGF) signaling, are widely used for renal cell carcinoma, including metastasis. In this study, we report a case of cardiovascular adverse events of aortic dissection and cardiac dysfunction during treatment with sorafenib and axitinib for metastatic renal cell carcinoma. A 66-year-old man had been administered sorafenib for 2 years after nephrectomy due to renal cell carcinoma. To control the progression of metastatic lung tumor, axitinib was started after sorafenib for four years. During the treatment, angiotensin II type 1 receptor blockers and Ca antagonists were used to strictly control the axitinib-induced hypertension and proteinuria. Aortic dissection and cardiac dysfunction occurred coincidentally. Considering the critical role of VEGF signaling in the homeostasis of the cardiovascular system, we speculated that the long-term use of axitinib and sorafenib directly influenced the initiation of aortic dissection and cardiac dysfunction. Although the precise mechanisms underlying the aortic dissection and cardiac dysfunction induced by angiogenesis inhibition are still elusive, onco-cardiologists and oncologists should pay careful attention to cardiovascular toxicity and complications in patients with cancer, particularly patients undergoing long-term cancer treatment.

Mechanism and Management of Cancer Chemotherapy-Induced Atherosclerosis

“…Long-term treatment with angiogenesis inhibitors for more than several years has been reported to cause aortic dissection. Adequate caution should thus be exercised with respect to cardiotoxicity affecting medium and large blood vessels 20 – 22 ) .…”

Aortic dissection in a patient treated with anlotinib for metastatic lung squamous cell carcinoma

“…This is the first report on aortic dissection potentially related to the treatment of anlotinib in advanced lung cancer. Previous studies have also shown that anti‐angiogenic monoclonal antibodies and small‐molecule TKI can lead to aortic dissection (Table ).…”

Dimethylarginine dimethylaminohydrolase-1 contributes to exercise-induced cardiac angiogenesis in mice

“…VEGF is a leading regulator of angiogenesis. A large amount of evidence has demonstrated that the VEGF signaling pathway could directly promote blood vessel formation (32,33). Thus, the results indicated that DDAH1 contributes to exercise-induced cardiac angiogenesis.…”