周期蛋白依赖性激酶4/6抑制剂相关肺毒性的文献分析  

Literature analysis of lung toxicity related to cyclin-dependent kinase 4/6 inhibitors

作　　者：赵俊[1] 刘广伟[1] 林玉燕 张小蕾[1] 倪倍倍[1] ZHAO Jun;LIU Guangwei;LIN Yuyan;ZHANG Xiaolei;NI Beibei(Dept.of Pharmacy,the Affiliated Hospital of Qingdao University,Shandong Qingdao 266003,China;Dept.of Pharmacy,Shenzhen Hospital of Guangzhou University of Chinese Medicine(Futian),Guangdong Shenzhen 518000,China)

机构地区：[1]青岛大学附属医院药学部,山东青岛266003 [2]广州中医药大学深圳医院(福田)药学部,广东深圳518000

出　　处：《中国药房》2023年第3期355-360,共6页China Pharmacy

基　　金：山东省自然科学基金青年项目(No.ZR2021QH205)。

摘　　要：目的 为临床合理使用周期蛋白依赖性激酶(CDK)4/6抑制剂提供参考。方法 计算机检索Web of Science、PubMed、SpringerLink、中国知网、万方数据与维普网等数据库中CDK4/6抑制剂相关肺毒性文献,采用Excel 2013软件进行统计分析。结果 共纳入12篇符合纳入与排除标准的文献,涉及13例患者,包括美国3例,日本3例,印度2例,以色列、西班牙、法国、澳大利亚、沙特阿拉伯各1例;均为女性患者,年龄在43~89岁之间;所使用的CDK4/6抑制剂类药物包括哌柏西利(8例)、阿贝西利(3例)、瑞博西利(2例)。患者用药后发生肺毒性的时间在1周~15个月不等,多数患者均以呼吸困难、胸闷、气短、干咳等症状为主诉入院,其肺毒性主要表现为间质性肺病、嗜酸性粒细胞性肺炎、纵隔和肺门结节样反应、药物性肺炎、弥漫性肺泡损伤、组织性肺炎等。其治疗时长最短为3周,最长为6个月,治疗措施包括停药、静脉使用抗菌药物、静脉使用全身类固醇、吸氧等;治疗后8例患者好转或康复,5例患者因病情恶化死亡。1例患者再次使用该类药物后又出现肺毒性,须永久停止使用该类药物。结论CDK4/6抑制剂相关肺毒性有导致死亡的可能,临床须早期判断、及时停药,并尽早采用给予患者全身类固醇、吸氧等治疗措施。OBJECTIVE To provide reference for rational use of cyclin-dependent kinase 4/6(CDK4/6) inhibitors.METHODS Retrieved from Web of Science, PubMed, SpringerLink, CNKI, Wanfang Data and VIP database, and so on, the literature about lung toxicity related to CDK4/6 inhibitors were collected and analyzed statistically with Excel 2013 software.RESULTS A total of 12 literature which met the inclusion and exclusion criteria were included;13 patients were involved, among which 3 cases were from the United States, 3 from Japan, 2 from India, and 1 from Israel, Spain, France, Australia and Saudi Arabia respectively;all patients were female, aged between 43-89 years, of whom 8 were treated with palbocicilib, 3 with abemacilib, and 2 with ribociclib. The lung toxicity of patients after medication occurred from 1 week to 15 months;the majority of patients were hospitalized with the symptom such as difficulty breathing, chest tightness, shortness of breath, dry cough, etc.The lung toxicity mainly manifested as interstitial lung disease, eosinophilic pneumonia, mediastinal and pulmonary granulomatous reaction, drug-induced pneumonia, diffuse alveolar damage, organizing pneumonia and so on. The shortest treatment duration was 3 weeks, and the longest was 6 months. The treatment measures included drug withdrawal, intravenous use of antibiotics, intravenous use of systemic steroids, oxygen inhalation, and so on;after treatment, 8 patients improved or recovered, and 5patients died due to deterioration. One patient developed lung toxicity again after reuse of such drugs and must stop drugs permanently. CONCLUSIONS Lung toxicity related to CDK4/6 inhibitors possibly cause mortality. It is necessary to make early judgment, stop the drug in time, and give patients systemic steroids, oxygen inhalation and other treatment measures as soon as possible.

关 键 词：周期蛋白依赖性激酶4/6抑制剂 肺毒性 药品不良反应 文献分析 

分 类 号：R969.3[医药卫生—药理学] R979.1[医药卫生—药学]