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

作者：O' Bryant Cindy L; Haluska Paul; Rosen Lee; Ramanathan Ramesh K; Venugopal Balaji; Leong Stephen; Boinpally Ramesh; Franke Amy; Witt Karsten; Evans Jevry; Belani Chandra; Eckhardt S Gail; Ramalingam Suresh

来源：Cancer Chemotherapy and Pharmacology, 2012, 69(3): 605-612.

DOI：10.1007/s00280-011-1733-6

• Erlotinib
• Hepatic function
• Pharmacokinetics
• Protein binding
• Safety

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 AHF). %26lt;br%26gt;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 stratiWed into an AHF cohort (total bilirubin %26lt;= upper limit of normal [ULN] and ALT/AST %26lt;= 1.5 X ULN) or a MHI cohort (Child-Pugh score of 7-9). The frequency of adverse events and laboratory changes were assessed. %26lt;br%26gt;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 mu g/mL and corresponding median AUC(0-t) 29.3 versus 30.5 mu g 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. %26lt;br%26gt;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%26apos; tolerability.

• 出版日期2012-3