Cardiovascular Toxicities with Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitors in Cancer Patients: A Meta-Analysis of 77 Randomized Controlled Trials

Clin Drug Investig. 2018 Dec;38(12):1109-1123. doi: 10.1007/s40261-018-0709-2.

Abstract

Background and objective: Use of the vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) has led to considerable improvements in the clinical outcome of patients with various tumor types. However, VEGFR-TKIs may be associated with increased incidence of cardiovascular toxicities. We conducted this meta-analysis to systematically review the risk of cardiovascular toxicities with VEGFR-TKIs in cancer patients.

Methods: The relevant studies of the randomized controlled trials in cancer patients treated with VEGFR-TKIs were retrieved and a systematic evaluation was conducted. EMBASE, MEDLINE, and PubMed were searched for articles published until April 2018.

Results: A total of 77 randomized controlled trials and 27,353 patients were included. The current meta-analysis suggests that the use of VEGFR-TKIs significantly increases the risk of developing cardiovascular toxicities, such as all-grade and high-grade hypertension, all-grade bleeding, and all-grade cardiac dysfunction. Hypertension was the most common cardiovascular toxicity. There was no significant increased risk of all-grade and high-grade thromboembolism, high-grade bleeding, and high-grade cardiac dysfunction associated with these agents.

Conclusions: The available data suggest that the use of VEGFR-TKIs is associated with a significantly increased risk of cardiovascular toxicities in cancer patients. Clinicians should be aware of this risk and perform regular cardiovascular monitoring.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Cardiotoxins / adverse effects*
  • Cardiotoxins / therapeutic use
  • Cardiovascular Diseases / chemically induced*
  • Cardiovascular Diseases / enzymology
  • Hemorrhage / chemically induced
  • Hemorrhage / enzymology
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Protein Kinase Inhibitors / adverse effects*
  • Protein Kinase Inhibitors / therapeutic use
  • Randomized Controlled Trials as Topic / methods*
  • Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors*
  • Receptors, Vascular Endothelial Growth Factor / metabolism
  • Risk Factors
  • Thromboembolism / chemically induced
  • Thromboembolism / enzymology

Substances

  • Cardiotoxins
  • Protein Kinase Inhibitors
  • Receptors, Vascular Endothelial Growth Factor