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Hepatotoxicity with vascular endothelial growth factor receptor tyrosine kinase inhibitors: A meta-analysis of

Pooja Ghatalia1, Youjin Je2, Nemer El Mouallem1

  • 1Department of Internal Medicine, University of Alabama at Birmingham (UAB), AL, United States.

Critical Reviews in Oncology/Hematology
|December 20, 2014
PubMed

Insights

Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) increase the risk of liver injury, including elevated liver enzymes and rare hepatic failure. This meta-analysis confirms VEGFR TKI-associated hepatotoxicity in cancer patients.

Area of Science:

  • Oncology
  • Pharmacology
  • Hepatology

Background:

  • Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) are crucial in cancer therapy.
  • Hepatotoxicity is a known adverse effect of VEGFR TKIs, but its relative risk requires precise quantification.

Purpose of the Study:

  • To conduct a meta-analysis of randomized controlled trials (RCTs).
  • To determine the relative risk (RR) of hepatotoxicity associated with VEGFR TKIs compared to non-TKI treatments.

Main Methods:

  • Systematic review and meta-analysis of 52 RCTs involving 18,282 patients.
  • Searched PubMed/Medline, conference abstracts, clinicaltrials.gov, and package inserts.
  • Calculated RRs for all-grade and high-grade elevations in ALT, AST, ALP, and bilirubin.

Main Results:

  • VEGFR TKIs significantly increased the risk of all-grade ALT (RR 1.57), AST (RR 1.57), and bilirubin (RR 1.55) elevation.
  • High-grade elevations in ALT (RR 1.66) and AST (RR 1.61) were also significantly increased.
  • The incidence of hepatic failure was 0.8% in patients receiving VEGFR TKIs.

Conclusions:

  • VEGFR TKIs are associated with a significant increase in the risk of liver enzyme elevations.
  • While rare, hepatic failure is a potential severe adverse event.
  • Clinical monitoring for hepatotoxicity is essential in patients treated with VEGFR TKIs.
Keywords:
ApprovedHepatotoxicityMeta-analysisTyrosine kinase inhibitorsVascular endothelial growth factor receptor

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