Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Biostatistics Section, Clinical Research Center, Chiba University Hospital, Chiba, Japan.
Thorac Cancer. 2020 Jun;11(6):1495-1502. doi: 10.1111/1759-7714.13416. Epub 2020 Apr 1.
If anaplastic lymphoma kinase (ALK) gene rearrangement in lung cancer is identified, ALK-tyrosine kinase inhibitors (ALK-TKIs) can be an effective treatment. However, the details of drug-induced lung injury (DILI) caused by ALK-TKI, which can be a serious side effect of ALK-TKIs, remains unclear. This study aimed to investigate the clinical features and the onset risk factors of DILI by ALK-TKIs in clinical practice.
The clinical features of 56 consecutive patients who received crizotinib, alectinib, and/or ceritinib at our hospital from 2012 to 2018 were retrospectively examined. Among these, patients diagnosed with DILI due to ALK-TKIs were evaluated in terms of clinical features and parameters. Each clinical parameter before the administration of ALK-TKIs was compared between the DILI onset group and the non-onset group.
A total of seven cases were diagnosed with DILI due to ALK-TKIs; no DILI-related deaths were observed. Chest computed tomography (CT) scan findings identified six patients with the organizing pneumonia (OP) pattern and one with the hypersensitivity pneumonia pattern. The onset of DILI was significantly different in patients age ≥ 64 years and with a creatinine clearance <80 mL/minute.
Extra caution for DILI due to ALK-TKIs may be needed when recommending ALK-TKIs for patients over 64 years of age, or with decreased renal function. CT images of the majority of patients with DILI by ALK-TKIs show an OP pattern.
Significant findings of the study: Extra caution is needed when recommending ALK-TKIs for patients over 64 years of age or those with decreased renal function. Computed tomography images of the majority of patients with DILI by ALK-TKIs show an OP pattern.
The same or a different ALK-TKI may be considered as a treatment option after the onset of DILI, based on careful judgment.
如果在肺癌中发现间变性淋巴瘤激酶（ALK）基因重排，可以使用 ALK 酪氨酸激酶抑制剂（ALK-TKI）进行有效治疗。然而，ALK-TKI 引起的药物性肝损伤（DILI）的细节，这可能是 ALK-TKI 的严重副作用，尚不清楚。本研究旨在探讨临床实践中 ALK-TKI 引起的 DILI 的临床特征和发病风险因素。
回顾性分析 2012 年至 2018 年我院 56 例连续接受克唑替尼、阿来替尼和/或塞瑞替尼治疗的患者的临床特征。其中，评估了因 ALK-TKIs 而导致 DILI 的患者的临床特征和参数。在使用 ALK-TKI 之前，比较了 DILI 发病组和非发病组的每个临床参数。
共有 7 例患者被诊断为因 ALK-TKIs 引起的 DILI，无与 DILI 相关的死亡。胸部计算机断层扫描（CT）发现 6 例患者表现为机化性肺炎（OP）模式，1 例表现为过敏性肺炎模式。DILI 的发病在年龄≥64 岁和肌酐清除率<80mL/min 的患者中存在显著差异。
对于年龄≥64 岁或肾功能下降的患者，在推荐使用 ALK-TKI 时应格外小心，以避免 DILI。ALK-TKI 引起的大多数 DILI 患者的 CT 图像表现为 OP 模式。
对于年龄≥64 岁或肾功能下降的患者，在推荐使用 ALK-TKI 时应格外小心。ALK-TKI 引起的大多数 DILI 患者的 CT 图像表现为 OP 模式。
在 DILI 发病后，可根据谨慎判断，考虑使用相同或不同的 ALK-TKI 作为治疗选择。
