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

O’Bryant, C.L. et al. (2012) An open-label study to describe pharmacokinetic parameters of erlotinib in patients with advanced solid tumors with adequate and moderately impaired hepatic function. Cancer Chemotherapy and Pharmacology, 69(3), pp. 605-612. (doi: 10.1007/s00280-011-1733-6)

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Abstract

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). <p/>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. <p/>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 AUC0−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. <p/>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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Venugopal, Dr Balaji
Authors: O’Bryant, C.L., Haluska, P., Rosen, L., Ramanathan, R.K., Venugopal, B., Leong, S., Boinpally, R., Franke, A., Witt, K., Evans, J., Belani, C., Eckhardt, S.G., and Ramalingam, S.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Cancer Chemotherapy and Pharmacology
ISSN:0344-5704
Published Online:22 September 2011

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