Factors affecting crizotinib-induced hepatotoxicity in non-small cell lung cancer patients
Factors affecting crizotinib-induced hepatotoxicity in non-small cell lung cancer patients
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DOI：
10.1007/s12032-018-1213-5
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发表时间：
2018-12-01
期刊：
影响因子：
3.4
通讯作者：
Gwak, Hye Sun
中科院分区：
文献类型：
--
作者：
Jung, Dasom;Han, Ji Min;Gwak, Hye Sun
克唑替尼是一种口服酪氨酸激酶抑制剂，用于间变性淋巴瘤激酶阳性非小细胞肺癌（NSCLC）患者。尽管克唑替尼诱导的肝毒性可能导致剂量降低或中断，从而影响患者的治疗，但尚无研究探讨克唑替尼诱导的肝毒性的因素。本研究旨在评价影响克唑替尼诱导肝毒性的因素。2012年2月至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。对各种因素进行了审查，包括性别、年龄、体重、身高、体表面积、基础疾病、吸烟史、基因突变和伴随药物。在153例患者中，克唑替尼诱导的I级或以上肝毒性的发生率为83%（n=127）。单变量分析显示，克唑替尼给药后28天内，肝脏疾病或HBV的存在对肝毒性有显著影响。肝病或HBV携带者的肝毒性时间风险是无肝病或HBV患者的2.3倍。使用H2-拮抗剂或H2-拮抗剂/质子泵抑制剂显示，与未使用这些药物的患者相比，发生肝毒性的时间风险为1.7倍。因此，建议密切监测肝功能，特别是在肝损害或使用抗酸分泌剂的患者中。
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.