Medical Oncology

, 35:154 | Cite as

Factors affecting crizotinib-induced hepatotoxicity in non-small cell lung cancer patients

  • Dasom Jung
  • Ji Min Han
  • Jeong Yee
  • Jae Youn Kim
  • Hye Sun GwakEmail author
Original Paper


Crizotinib is an orally available tyrosine kinase inhibitor for patients with anaplastic lymphoma kinase-positive non-small cell lung cancer (NSCLC). Despite that crizotinib-induced hepatotoxicity may cause a dose reduction or interruption that can affect the patient’s treatment, there is no study to investigate factors for crizotinib-induced hepatotoxicity. The purpose of this study was to evaluate factors affecting crizotinib-induced hepatotoxicity. From February 2012 to April 2018, a retrospective study was performed on NSCLC patients treated with crizotinib. Various factors were reviewed including sex, age, body weight, height, body surface area, underlying disease, smoking history, genetic mutation, and concomitant drugs. Among 153 patients, incidence of crizotinib-induced hepatotoxicity of grade I or higher was 83% (n = 127). The presence of liver disease or HBV revealed significant effect on hepatotoxicity within 28 days after crizotinib administration in univariate analysis. Patients with liver disease or HBV carriers revealed 2.3 times the hazard of time to hepatotoxicity compared to those without liver disease or HBV. Use of H2-antagonist or H2-antagonist/proton pump inhibitor revealed 1.7 times the hazard of time to hepatotoxicity compared to those that did not use those medications. Thus, close monitoring of liver function is recommended, especially in patients with liver impairment or using anti-acid secreting agents.


Crizotinib Hepatotoxicity Time to reach hepatotoxicity H2-antagonist Proton pump inhibitor Presence of liver disease or hepatitis B virus 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required.

Informed consent

The Asan Medical Center Clinical Research Ethics Committee approved this study and waived the requirement for informed consent due to the retrospective nature of the study with collection of anonymous-subject data (IRB Number: 2018-0339).


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Graduate School of Converging Clinical & Public HealthEwha Womans UniversitySeoulRepublic of Korea
  2. 2.Department of PharmacyAsan Medical CenterSeoulRepublic of Korea
  3. 3.College of Pharmacy and Division of Life and Pharmaceutical SciencesEwha Womans UniversitySeoulRepublic of Korea

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