The Impact of Pazopanib on the Cardiovascular System

J Cardiovasc Pharmacol Ther. 2018 Sep;23(5):387-398. doi: 10.1177/1074248418769612. Epub 2018 Apr 29.

Abstract

Pazopanib is an approved treatment for renal cell carcinoma and a second-line treatment for nonadipocytic soft-tissue sarcoma. However, its clinical efficacy is limited by its cardiovascular side effects. Pazopanib and other vascular endothelial growth factor receptor tyrosine kinase inhibitors have been associated with the development of hypertension, QT interval prolongation, and other cardiovascular events; however, these mechanisms are largely unknown. Gaining a deeper understanding of these mechanisms is essential for the development of appropriate surveillance strategies and possible diagnostic biomarkers to allow us to monitor patients and modulate therapy prior to significant cardiac insult. This approach will be vital in keeping patients on these life-saving therapies and may be applicable to other tyrosine kinase inhibitors as well. In this review, we provide a comprehensive overview of the preclinical and clinical side effects of pazopanib with a focus on the mechanisms responsible for its toxicity to the cardiovascular system.

Keywords: hypertension; pazopanib; renal cell carcinoma; tyrosine kinase inhibitors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiogenesis Inhibitors / adverse effects*
  • Angiogenesis Inhibitors / pharmacokinetics
  • Animals
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / pathology
  • Cardiovascular Diseases / chemically induced*
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / physiopathology
  • Cardiovascular System / drug effects*
  • Cardiovascular System / physiopathology
  • Humans
  • Indazoles
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / pathology
  • Pyrimidines / adverse effects*
  • Pyrimidines / pharmacokinetics
  • Risk Assessment
  • Risk Factors
  • Sarcoma / drug therapy*
  • Sarcoma / pathology
  • Soft Tissue Neoplasms / drug therapy*
  • Soft Tissue Neoplasms / pathology
  • Sulfonamides / adverse effects*
  • Sulfonamides / pharmacokinetics
  • Treatment Outcome

Substances

  • Angiogenesis Inhibitors
  • Indazoles
  • Pyrimidines
  • Sulfonamides
  • pazopanib