日本非小细胞肺癌患者中影响表皮生长因子受体酪氨酸激酶抑制剂所致肝毒性的因素评估：一项双中心回顾性研究
Evaluation of factors affecting epidermal growth factor receptor tyrosine kinase inhibitor-induced hepatotoxicity in Japanese patients with non-small cell lung cancer: a two-center retrospective study.
作者信息
Nagai Hirofumi, Shimada Tsutomu, Takahashi Yoshimitsu, Nishikawa Mikako, Tozuka Hiroyuki, Yamamoto Yasuto, Niwa Osamu, Takahara Yutaka, Fujita Arimi, Nagase Katsuhiko, Kasahara Kazuo, Yano Seiji, Sai Yoshimichi
机构信息
Department of Clinical Pharmacokinetics, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan.
Department of Hospital Pharmacy, University Hospital, Kanazawa Medical University, 1-1 Daigaku, Uchinada-machi, Kahoku-gun, Ishikawa, 920-0293, Japan.
出版信息
J Pharm Health Care Sci. 2022 Dec 1;8(1):28. doi: 10.1186/s40780-022-00258-7.
BACKGROUND
Gefitinib and erlotinib, are epidermal growth factor receptor tyrosine kinase inhibitors, and are currently recommended for non-small cell lung cancer stage IV in the elderly and in patients with decreased performance status in the Japanese Lung Cancer Society Guideline, but they occasionally caused severe hepatotoxicity requiring postponement or modification of treatment. However, little is known about the risk factors for hepatotoxicity in patients receiving gefitinib and erlotinib. In this study, we investigated the factors influencing hepatotoxicity in Japanese non-small cell lung cancer (NSCLC) patients treated with gefitinib or erlotinib monotherapy.
METHODS
Japanese patients with NSCLC who started gefitinib or erlotinib monotherapy from January 2005 to December 2017 at Kanazawa University Hospital or Kanazawa Medical University Hospital were included in this study. Factors affecting hepatotoxicity were retrospectively investigated by multiple logistic regression analysis.
RESULTS
A total of 102 patients who received gefitinib and 95 patients who received erlotinib were included in the analysis. In the gefitinib group, a body mass index (BMI) ≥ 25 was associated with an increased risk of hepatotoxicity (OR = 4.571, 95% CI = 1.486-14.056, P = 0.008). In the erlotinib group, concomitant use of acid-suppressing medications (AS), namely proton pump inhibitors or histamine-2 receptor antagonists, was associated with a reduced risk of hepatotoxicity (OR = 0.341, 95% CI = 0.129-0.900, P = 0.030).
CONCLUSIONS
BMI ≥ 25 in patients treated with gefitinib increased the risk of hepatotoxicity. In contrast, AS combination with erlotinib reduced the risk of hepatotoxicity. Thus, because different factors influence the risk of hepatotoxicity, monitoring for adverse events should take into account patient background factors and concomitant medications.
背景
吉非替尼和厄洛替尼是表皮生长因子受体酪氨酸激酶抑制剂，在日本肺癌学会指南中，目前推荐用于老年非小细胞肺癌IV期患者及体能状态下降的患者，但它们偶尔会引起严重肝毒性，需要推迟或调整治疗。然而，对于接受吉非替尼和厄洛替尼治疗的患者发生肝毒性的危险因素知之甚少。在本研究中，我们调查了接受吉非替尼或厄洛替尼单药治疗的日本非小细胞肺癌（NSCLC）患者中影响肝毒性的因素。
方法
本研究纳入了2005年1月至2017年12月在金泽大学医院或金泽医科大学医院开始接受吉非替尼或厄洛替尼单药治疗的日本NSCLC患者。通过多因素逻辑回归分析对影响肝毒性的因素进行回顾性研究。
结果
分析共纳入102例接受吉非替尼治疗的患者和95例接受厄洛替尼治疗的患者。在吉非替尼组中，体重指数（BMI）≥25与肝毒性风险增加相关（OR = 4.571，95%CI = 1.486 - 14.056，P = 0.008）。在厄洛替尼组中，同时使用抑酸药物（AS），即质子泵抑制剂或组胺-2受体拮抗剂，与肝毒性风险降低相关（OR = 0.341，95%CI = 0.129 - 0.900，P = 0.030）。
结论
接受吉非替尼治疗的患者BMI≥25会增加肝毒性风险。相比之下，AS与厄洛替尼联合使用可降低肝毒性风险。因此，由于不同因素影响肝毒性风险，不良事件监测应考虑患者背景因素和同时使用的药物。
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