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

Cindy L. O'Bryant, Paul Haluska, Lee Rosen, Ramesk K Ramanathan, Balaji Venugopal, Stephen Leong, Ramesh Boinpally, Amy Franke, Karsten Witt, Jeffry Evans, Chandra Belani, S. Gail Eckhardt, Suresh Ramalingam

Research output: Contribution to journalArticle

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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). 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.

Original languageEnglish (US)
Pages (from-to)605-612
Number of pages8
JournalCancer Chemotherapy and Pharmacology
Volume69
Issue number3
DOIs
StatePublished - Mar 2012

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Pharmacokinetics
Labels
Tumors
Liver
Neoplasms
Erlotinib Hydrochloride
Bilirubin
Safety
Sampling
Plasmas
Area Under Curve

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Toxicology

Cite this

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, Cindy L.; Haluska, Paul; Rosen, Lee; Ramanathan, Ramesk K; Venugopal, Balaji; Leong, Stephen; Boinpally, Ramesh; Franke, Amy; Witt, Karsten; Evans, Jeffry; Belani, Chandra; Gail Eckhardt, S.; Ramalingam, Suresh.

In: Cancer Chemotherapy and Pharmacology, Vol. 69, No. 3, 03.2012, p. 605-612.

Research output: Contribution to journalArticle

O'Bryant, CL, Haluska, P, Rosen, L, Ramanathan, RK, Venugopal, B, Leong, S, Boinpally, R, Franke, A, Witt, K, Evans, J, Belani, C, Gail Eckhardt, S & Ramalingam, S 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, vol. 69, no. 3, pp. 605-612. https://doi.org/10.1007/s00280-011-1733-6
O'Bryant, Cindy L. ; Haluska, Paul ; Rosen, Lee ; Ramanathan, Ramesk K ; Venugopal, Balaji ; Leong, Stephen ; Boinpally, Ramesh ; Franke, Amy ; Witt, Karsten ; Evans, Jeffry ; Belani, Chandra ; Gail Eckhardt, S. ; Ramalingam, Suresh. / An open-label study to describe pharmacokinetic parameters of erlotinib in patients with advanced solid tumors with adequate and moderately impaired hepatic function. In: Cancer Chemotherapy and Pharmacology. 2012 ; Vol. 69, No. 3. pp. 605-612.
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AU - O'Bryant, Cindy L.

AU - Haluska, Paul

AU - Rosen, Lee

AU - Ramanathan, Ramesk K

AU - Venugopal, Balaji

AU - Leong, Stephen

AU - Boinpally, Ramesh

AU - Franke, Amy

AU - Witt, Karsten

AU - Evans, Jeffry

AU - Belani, Chandra

AU - Gail Eckhardt, S.

AU - Ramalingam, Suresh

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N2 - 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.

AB - 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.

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KW - Protein binding

KW - Safety

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