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

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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 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.

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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Fig. 1

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Abbreviations

AHF:

Adequate hepatic function

MHI:

Moderate hepatic impairment

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Acknowledgments

The Grant support for this study is given by OSI Pharmaceuticals, Inc. (Boulder, CO).

Author information

Authors and Affiliations

  1. 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 L. O’Bryant

  2. Mayo Clinic, Rochester, MN, USA

    Paul Haluska

  3. Premiere Oncology, Santa Monica, CA, USA

    Lee Rosen

  4. University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA

    Ramesh K. Ramanathan, Chandra Belani & Suresh Ramalingam

  5. Beatson Oncology Centre, University of Glasgow, Glasgow, UK

    Balaji Venugopal & Jeffry Evans

  6. University of Colorado Cancer Center, Aurora, CO, USA

    Stephen Leong & S. Gail Eckhardt

  7. OSI Pharmaceuticals, Inc, Boulder, CO, USA

    Ramesh Boinpally, Amy Franke & Karsten Witt

Authors
  1. Cindy L. O’Bryant
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  2. Paul Haluska
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  3. Lee Rosen
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  4. Ramesh K. Ramanathan
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  5. Balaji Venugopal
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  6. Stephen Leong
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  7. Ramesh Boinpally
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  8. Amy Franke
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  9. Karsten Witt
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  10. Jeffry Evans
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  11. Chandra Belani
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  12. S. Gail Eckhardt
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  13. Suresh Ramalingam
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Corresponding author

Correspondence to Cindy L. O’Bryant.

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O’Bryant, C.L., Haluska, P., Rosen, L. et al. 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 69, 605–612 (2012). https://doi.org/10.1007/s00280-011-1733-6

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  • DOI: https://doi.org/10.1007/s00280-011-1733-6

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