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

Int Heart J. 2018 Sep 26;59(5):1174-1179. doi: 10.1536/ihj.17-461. Epub 2018 Aug 29.

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.

Keywords: Axitinib; Cancer therapeutics-related cardiac dysfunction; Cardiovascular toxicity; Onco-cardiology/cardio-oncology; Sorafenib; VEGF signaling pathway.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Angiogenesis Inhibitors / adverse effects*
  • Aortic Dissection / chemically induced*
  • Aortic Dissection / complications
  • Axitinib
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / pathology
  • Carcinoma, Renal Cell / surgery
  • Heart Diseases / chemically induced*
  • Heart Diseases / complications
  • Heart Diseases / physiopathology
  • Humans
  • Imidazoles / administration & dosage
  • Imidazoles / adverse effects*
  • Imidazoles / therapeutic use
  • Indazoles / administration & dosage
  • Indazoles / adverse effects*
  • Indazoles / therapeutic use
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / pathology
  • Kidney Neoplasms / surgery
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / pathology
  • Lung Neoplasms / secondary*
  • Male
  • Neoplasm Metastasis
  • Niacinamide / administration & dosage
  • Niacinamide / adverse effects
  • Niacinamide / analogs & derivatives*
  • Niacinamide / therapeutic use
  • Phenylurea Compounds / administration & dosage
  • Phenylurea Compounds / adverse effects*
  • Phenylurea Compounds / therapeutic use
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use
  • Sorafenib
  • Vascular Endothelial Growth Factor A / drug effects
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Angiogenesis Inhibitors
  • Imidazoles
  • Indazoles
  • Phenylurea Compounds
  • Protein Kinase Inhibitors
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Niacinamide
  • Sorafenib
  • Axitinib