title: Hepatotoxicity with vascular endothelial growth factor receptor tyrosine kinase inhibitors: A meta-analysis of randomized clinical trials.
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%.
authors.affiliation: Department of Internal Medicine, University of Alabama at Birmingham (UAB), AL, United States.
authors.forename: Pooja
authors.initials: P
authors.lastname: Ghatalia
authors.affiliation: Department of Food and Nutrition, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Youjin
authors.initials: Y
authors.lastname: Je
authors.affiliation: Department of Internal Medicine, University of Alabama at Birmingham (UAB), AL, United States.
authors.forename: Nemer El
authors.initials: NE
authors.lastname: Mouallem
authors.affiliation: Dana Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, United States.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Nguyen
authors.affiliation: Dana Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, United States.
authors.forename: Quoc-Dien
authors.initials: QD
authors.lastname: Trinh
authors.affiliation: Department of Internal Medicine, Section of Medical Oncology, UAB Medical Center, United States. Electronic address: gsonpavde@uabmc.edu.
authors.forename: Guru
authors.initials: G
authors.lastname: Sonpavde
authors.affiliation: Dana Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, United States. Electronic address: toni_choueiri@dfci.harvard.edu.
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis* / Q000453:epidemiology / Q000378:metabolism*; D006801:Humans; D015994:Incidence; D008111:Liver Function Tests; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy; D016017:Odds Ratio; D063868:Patient Outcome Assessment; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D012306:Risk
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D040262:Receptors, Vascular Endothelial Growth Factor
keywords: Approved; Hepatotoxicity; Meta-analysis; Tyrosine kinase inhibitors; Vascular endothelial growth factor receptor