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

Crit Rev Oncol Hematol. 2015 Mar;93(3):257-76. doi: 10.1016/j.critrevonc.2014.11.006. Epub 2014 Nov 27.

Abstract

A meta-analysis of randomized controlled trials (RCT) was conducted to determine the relative risk (RR) of hepatotoxicity with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKI). Citations from PubMed/Medline, abstracts from major conferences, clinicaltrials.gov and package inserts were reviewed to include RCTs comparing arms with or without a VEGFR TKI. The RRs of all-grade ALT, AST, ALP and bilirubin elevation in 18,282 patients from 52 trials were 1.57 (95% CI 1.38-1.79, p<0.001), 1.57 (95% CI 1.36-1.81, p<0.001), 1.20 (95% CI 1.09-1.83, p<0.001) and 1.55 (95% CI 1.21-1.97, p<0.001) respectively, and high-grade elevations were 1.66 (95% CI 1.25-2.20, p=0.001), 1.61 (95% CI 1.21-2.14, p=0.001), 1.02 (95% CI 0.70-1.47, p=0.932) and 1.34 (95% CI 1.0-1.81, p=0.054) respectively compared to those in the non-TKI group. The incidence of hepatic failure with VEGFR TKIs was 0.8%.

Keywords: Approved; Hepatotoxicity; Meta-analysis; Tyrosine kinase inhibitors; Vascular endothelial growth factor receptor.

Publication types

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

MeSH terms

  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Chemical and Drug Induced Liver Injury / diagnosis*
  • Chemical and Drug Induced Liver Injury / epidemiology
  • Chemical and Drug Induced Liver Injury / metabolism*
  • Humans
  • Incidence
  • Liver Function Tests
  • Neoplasms / complications
  • Neoplasms / drug therapy
  • Odds Ratio
  • Patient Outcome Assessment
  • Protein Kinase Inhibitors / adverse effects*
  • Protein Kinase Inhibitors / therapeutic use
  • Randomized Controlled Trials as Topic
  • Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors*
  • Risk

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Receptors, Vascular Endothelial Growth Factor