An open-label study to describe pharmacokinetic parameters of erlotinib in patients with advanced solid tumors with adequate and moderately impaired hepatic function

Cancer Chemother Pharmacol. 2012 Mar;69(3):605-12. doi: 10.1007/s00280-011-1733-6. Epub 2011 Sep 22.


Purpose: To compare the pharmacokinetic (PK) parameters of a single dose of erlotinib in cancer patients with moderate hepatic impairment (MHI) to those of cancer patients with adequate hepatic function (AHF).

Methods: Cancer patients with either AHF or MHI were treated with a single 150 mg dose of erlotinib on day 1 only followed by 96 h of plasma sampling for PK assessment. From day 5, patients were allowed to continue daily erlotinib in a maintenance phase. Non-smoking patients were stratified into an AHF cohort (total bilirubin ≤ upper limit of normal [ULN] and ALT/AST ≤ 1.5 X ULN) or a MHI cohort (Child-Pugh score of 7-9). The frequency of adverse events and laboratory changes were assessed.

Results: Thirty-six patients, 21 with AHF and 15 with MHI, received at least one dose of erlotinib. The PK of erlotinib was similar between the two cohorts with a median C (max) of 1.09 versus 0.828 μg/mL and corresponding median AUC(0-t ) 29.3 versus 30.5 μg h/mL for the AHF and MHI cohorts, respectively. Adverse events from erlotinib in cancer patients with MHI were consistent with the known safety profile.

Conclusions: The PK and safety profiles of erlotinib in patients with MHI were similar to those with AHF. As a result, a reduced starting dose of erlotinib in patients with MHI is not required and treatment should be guided by patients' tolerability.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / blood
  • Antineoplastic Agents / pharmacokinetics*
  • Antineoplastic Agents / therapeutic use
  • Cohort Studies
  • Dose-Response Relationship, Drug
  • ErbB Receptors / antagonists & inhibitors
  • Erlotinib Hydrochloride
  • Female
  • Humans
  • Liver / drug effects
  • Liver / metabolism
  • Liver / physiopathology*
  • Liver Function Tests
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neoplasms / physiopathology
  • Protein Binding
  • Quinazolines / adverse effects
  • Quinazolines / blood
  • Quinazolines / pharmacokinetics*
  • Quinazolines / therapeutic use


  • Antineoplastic Agents
  • Quinazolines
  • Erlotinib Hydrochloride
  • EGFR protein, human
  • ErbB Receptors