title: An open-label study to describe pharmacokinetic parameters of erlotinib in patients with advanced solid tumors with adequate and moderately impaired hepatic function.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, University of Colorado Cancer Center, Mail Stop C238, 12850 East Montview Blvd., V20-1223, Aurora, CO, 80045, USA. Cindy.OBryant@ucdenver.edu
authors.forename: Cindy L
authors.initials: CL
authors.lastname: O'Bryant
authors.forename: Paul
authors.initials: P
authors.lastname: Haluska
authors.forename: Lee
authors.initials: L
authors.lastname: Rosen
authors.forename: Ramesh K
authors.initials: RK
authors.lastname: Ramanathan
authors.forename: Balaji
authors.initials: B
authors.lastname: Venugopal
authors.forename: Stephen
authors.initials: S
authors.lastname: Leong
authors.forename: Ramesh
authors.initials: R
authors.lastname: Boinpally
authors.forename: Amy
authors.initials: A
authors.lastname: Franke
authors.forename: Karsten
authors.initials: K
authors.lastname: Witt
authors.forename: Jeffry
authors.initials: J
authors.lastname: Evans
authors.forename: Chandra
authors.initials: C
authors.lastname: Belani
authors.forename: S
authors.initials: S
authors.lastname: Gail Eckhardt
authors.forename: Suresh
authors.initials: S
authors.lastname: Ramalingam
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011485:Protein Binding; D011799:Quinazolines / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors