Graduate School of Converging Clinical & Public Health, Ewha Womans University, Seoul, 03760, Republic of Korea.
Department of Pharmacy, Asan Medical Center, Seoul, 05505, Republic of Korea.
Med Oncol. 2018 Oct 26;35(12):154. doi: 10.1007/s12032-018-1213-5.
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.
克唑替尼是一种可口服的酪氨酸激酶抑制剂，适用于间变性淋巴瘤激酶阳性的非小细胞肺癌（NSCLC）患者。尽管克唑替尼引起的肝毒性可能导致剂量减少或中断，从而影响患者的治疗，但目前尚无研究探讨克唑替尼引起肝毒性的相关因素。本研究旨在评估影响克唑替尼引起肝毒性的因素。从 2012 年 2 月到 2018 年 4 月，对接受克唑替尼治疗的 NSCLC 患者进行了一项回顾性研究。回顾了包括性别、年龄、体重、身高、体表面积、基础疾病、吸烟史、基因突变和合并用药在内的各种因素。在 153 例患者中，克唑替尼引起的肝毒性 I 级或更高级别的发生率为 83%（n=127）。单因素分析显示，在克唑替尼给药后 28 天内，存在肝脏疾病或 HBV 对肝毒性有显著影响。与无肝脏疾病或 HBV 携带者相比，有肝脏疾病或 HBV 携带者的患者发生肝毒性的风险增加 2.3 倍。与未使用这些药物的患者相比，使用 H2 拮抗剂或 H2 拮抗剂/质子泵抑制剂的患者发生肝毒性的风险增加 1.7 倍。因此，建议密切监测肝功能，尤其是在有肝损伤或使用抗酸分泌剂的患者中。
