Risk factors associated with the incidence and time to onset of lapatinib-induced hepatotoxicity
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Although lapatinib-induced hepatotoxicity can cause severe clinical complications in patients, the factors affecting hepatotoxicity have rarely been investigated. The purpose of this study was to investigate risk factors for hepatotoxicity and time to lapatinib-induced hepatotoxicity.
This retrospective study was performed on metastatic breast cancer patients treated with lapatinib. Various factors were evaluated for hepatotoxicity and time to hepatotoxicity, including sex, age, body weight, height, body surface area, underlying disease, smoking history, start dose of lapatinib, status of liver metastasis, and concomitant drugs.
Among 159 patients, the percentage of patients with hepatotoxicity after lapatinib initiation was 57.9% (n = 92). Multivariate analysis showed that concomitant use of H2 blockers increased the incidence of hepatotoxicity by 2.3-fold. Patients who received CYP3A4 inducers had 3.1 times higher risk of hepatotoxicity incidence; the attributable risks of H2 blockers and CYP3A4 inducers were 56.7% and 68.1%, respectively. Use of H2 blockers increased the hazard of time to hepatotoxicity by 1.8-fold compared to non-use of H2 blockers.
Our study demonstrated that concomitant use of H2 blockers and CYP3A4 inducers was associated with lapatinib-induced hepatotoxicity. Close liver function monitoring is recommended, especially in patients receiving H2 blockers or CYP3A4 inducers.
KeywordsLapatinib Hepatotoxicity H2 blocker CYP3A4 inducer
JYM, JMH, and HSG contributed to the study conception and design. Material preparation and data collection were performed by JYM, JMH, and IS. Data analysis and interpretation were performed by JYM, JMH, and IS. The manuscript was written by JYM and JMH. The manuscript was revised by HSG. All authors reviewed and approved the final manuscript.
Compliance with ethical standards
Conflicts of interest
The authors declare that they have no conflict of interest.
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.
This study was approved by the Institutional Review Board of National Cancer Center, Korea (IRB number: NCC 2019-0091), and the requirement for obtaining informed consent was waived due to the retrospective nature of this study.
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