title: Does the use of lapatinib increase the risk of fatigue and hepatic toxicities in patients with solid tumors? A critical literature review and meta-analysis.
abstract: OBJECTIVE
  A systematic review and meta-analysis of fatigue and hepatic adverse events associated with lapatinib use in solid tumor patients were performed.
  
  
  METHODS
  Eligible studies included randomized Phase II and III trials of patients with solid tumors taking lapatinib. They described events of fatigue, elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin. Our search yielded 380 potentially relevant citations on lapatinib from PubMed/Medline, CENTRAL Cochrane registry and ASCO meeting library.
  
  
  RESULTS
  After exclusion of ineligible studies, a total of 15 clinical trials were included in the meta-analysis. The relative risk (RR) of all-grade fatigue, elevated ALT, AST and total bilirubin were 0.99 (95% CI 0.87 - 1.13; p = 0.87), 1.12 (95% CI 0.87 - 1.44; p = 0.55), 0.79 (95% CI 0.43 - 1.45; p = 0.44), 5.17 (95% CI 0.18 - 149.81; p = 0.34), respectively. Exploratory subgroup analysis showed no effect of comparator regimen on the RR of the relevant adverse events.
  
  
  CONCLUSIONS
  This meta-analysis demonstrated that the evidence for a true increased risk of hepatotoxicity or fatigue with lapatinib-based treatment compared to control is not yet fully convincing. Future studies should investigate this risk further. Clinicians must be aware of these risks and perform regular clinical monitoring.
authors.affiliation: Ain Shams University, Clinical Oncology Department, Faculty of Medicine , Lotfy Elsayed street, Cairo, 11665 , Egypt +20 33028656 ; omar.abdelrhman@med.asu.edu.eg.
authors.forename: Omar
authors.initials: O
authors.lastname: Abdel-Rahman
authors.forename: Mona
authors.initials: M
authors.lastname: Fouad
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology / Q000209:etiology*; D005221:Fatigue / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D000077341:Lapatinib; D009369:Neoplasms / Q000188:drug therapy; D011799:Quinazolines / Q000009:adverse effects* / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012306:Risk
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D000077341:Lapatinib
keywords: fatigue; hepatotoxicity; lapatinib; meta-analysis