416例吉非替尼不良反应病例回顾分析  

Systematic review and analysis of 416 cases of adverse drug reactions induced by gefitinib

作　　者：安鹏姣 杨莉萍[1] AN Peng-jiao;YANG Li-ping(Department of Pharmacy,Beijing Hospital,National Center of Gerontology,Institute of Geriatric Medicine,Chinese Academy of Medical Sciences,Beijing 100730,China;Department of Pharmacy Administration&Clinical Pharmacy,School of Pharmaceutical Sciences,Peking University,Beijing 100191,China)

机构地区：[1]北京医院国家老年医学中心药学部,药物临床风险与个体化应用评价北京市重点实验室,北京100730 [2]北京大学药学院药事管理与临床药学系,北京100191

出　　处：《中国医院药学杂志》2021年第7期716-723,共8页Chinese Journal of Hospital Pharmacy

摘　　要：目的:对接受表皮生长因子受体(epidermal growth factor receptor, EGFR)抑制剂吉非替尼治疗的癌症患者发生药物不良反应(adverse drug reactions, ADR)的病例报告进行系统回顾,分析死亡危险因素及对策。方法:对PubMed、Embase、Cochrane图书馆、CINAHL、CNKI、WanFang数据、VIP和SinoMed等数据库进行检索,检索时间从建库至2018年12月31日。由2名研究者独立进行数据筛选和提取并根据纳入及排除标准进行交叉核对。使用IBM SPSS Statistics 25进行单因素分析和Logistic回归分析。结果:最终纳入345篇病例报告,共计416例患者。大部分患者为女性(54.6%)、亚洲人(82.5%)、患肺腺癌(68.3%)、无吸烟史(62.6%)。仅150例患者报道了基因突变信息。ADR最常见的部位依次是皮肤、消化道、肺、肝脏、肾脏和泌尿系统及血液系统。统计发现有心肌病(n=2)和心肌梗死(n=2)等4例说明书中未提及的ADR。32例患者发生ADR相关死亡,其中有23例与肺部ADR有关,最短死亡时间为2 d[中位时间11 d,四分位数间距(interquartile distance, IQR)为(4,22)d]。单因素分析和Logistic回归分析表明,年龄>70岁和发生ADR后不停用吉非替尼是肺部ADR死亡相关的危险因素。结论:吉非替尼的临床应用存在基因检测不足和超适应症应用的情况。吉非替尼引起的肺部ADR发展迅速、病程短,应注意监测70岁以上老年患者的影像学表现和新发症状。尽管存在治疗肿瘤和处理ADR的主次矛盾,发生肺部ADR后及时停药处理更可能降低死亡风险。此外还应警惕EGFR抑制剂引起的罕见且致命的心脏ADR。OBJECTIVE To evaluate the safety of gefitinib based upon a systematic review of case reports describing adverse drug reactions(ADR) in cancer patients.METHODS Systematical searching was performed for the literatures as of August 31 st, 2019 and individual data extracted from case reports were analyzed with IBM SPSS Statistics 25.RESULTS A total of 345 cases reports or series involving 416 cases were included. Most patients are female(54.6%), Asian(82.5%), having lung adenocarcinoma(68.3%) and without a smoking history(62.6%). And 150 cases provided information on gene mutations. Cardiomyopathy(n=2) and myocardial infarction(n=2) were new ADR not mentioned in labeling. The most commonly involved organs or systems were skin, liver, digestive tract, lung, urinary system and blood system. Among 32 cases of ADR related death, 23 cases died of pulmonary lesions. The minimal interval from the occurrence of pulmonary ADR to death was 2 days with a median of 11 days[interquartile distance(IQR)(4, 22) days]. Univariate and Logistic regression analyses indicated that age over 70 years and continuation of gefitinib after ADR were risk factors of pulmonary ADR related death.CONCLUSION The clinical applications of gefitinib are often off-label and without gene mutation detection. Gefitinib may cause fatal cardiac ADR. Severe pulmonary lesion occurs more quickly than we assumed and causes a serious threat to patient life. Patients aged over 70 years should be carefully monitored by newly emerging pulmonary imaging features and clinical symptoms. And gefitinib should be discontinued once pulmonary lesion occurs to reduce fatal risks.

关 键 词：吉非替尼 病例报告 药物不良反应 肺毒性 系统回顾 

分 类 号：R979.1[医药卫生—药品]