CAJ | 학술논문

目的探讨吉非替尼／厄洛替尼所致间质性肺疾病（ ILD）患者的临床特点与预后。方法以“表皮生长因子受体酪氨酸激酶抑制剂”“吉非替尼”“厄洛替尼”“间质性肺疾病”“个案报道”以及相应的英文词汇为关键词，检索中国期刊全文数据库、万方数据库、维普数据库、中国生物医学文献数据库、PubMed、MEDLINE和Web of Science（2000年1月至2014年4月），收集吉非替尼／厄洛替尼致ILD的个案报道，记录患者的年龄、性别、病理诊断与分期、既往病史、既往治疗史、、ILD发生时间、临床表现、治疗及转归等。结果共筛选出有效文献40篇，计60例患者。其中59例为非小细胞肺癌，1例为胰腺体尾部癌。使用吉非替尼者35例（58.3％），剂量为250 mg／d 者34例、500 mg／d者1例；使用厄洛替尼者25例（41.7％），剂量均为150 mg／d。ILD的发生时间最短为用药后1 d，最长为用药后210 d，33例（55.0％）发生在用药后7~28 d。吉非替尼／厄洛替尼所致ILD的主要临床表现为呼吸困难、咳嗽、发热。同时出现皮疹者10例（16.7％），出现腹泻和肝损伤者各2例（各3.3％）。确诊为吉非替尼／厄洛替尼所致ILD后均立即停药并采取对症和激素疗法，30例治疗3~90 d（中位数10 d）后临床症状及影像学表现好转，30例治疗1~80 d（中位数6 d）后死亡。用药后出现ILD时间＜7 d、既往有肺纤维化和放射性肺炎病史以及同时出现肝损伤者（分别为4、2、2例）均死亡。结论吉非替尼／厄洛替尼致ILD的中位时间为24 d（1~210 d），主要临床表现为呼吸困难、咳嗽、发热，用药7 d内出现ILD、有肺纤维化和放射性肺炎病既往史者、同时出现肝损伤者预后不佳。本结论源于个案报道，有一定局限性。
목적탐토길비체니／액락체니소치간질성폐질병（ ILD）환자적림상특점여예후。방법이“표피생장인자수체락안산격매억제제”“길비체니”“액락체니”“간질성폐질병”“개안보도”이급상응적영문사회위관건사，검색중국기간전문수거고、만방수거고、유보수거고、중국생물의학문헌수거고、PubMed、MEDLINE화Web of Science（2000년1월지2014년4월），수집길비체니／액락체니치ILD적개안보도，기록환자적년령、성별、병리진단여분기、기왕병사、기왕치료사、、ILD발생시간、림상표현、치료급전귀등。결과공사선출유효문헌40편，계60례환자。기중59례위비소세포폐암，1례위이선체미부암。사용길비체니자35례（58.3％），제량위250 mg／d 자34례、500 mg／d자1례；사용액락체니자25례（41.7％），제량균위150 mg／d。ILD적발생시간최단위용약후1 d，최장위용약후210 d，33례（55.0％）발생재용약후7~28 d。길비체니／액락체니소치ILD적주요림상표현위호흡곤난、해수、발열。동시출현피진자10례（16.7％），출현복사화간손상자각2례（각3.3％）。학진위길비체니／액락체니소치ILD후균립즉정약병채취대증화격소요법，30례치료3~90 d（중위수10 d）후림상증상급영상학표현호전，30례치료1~80 d（중위수6 d）후사망。용약후출현ILD시간＜7 d、기왕유폐섬유화화방사성폐염병사이급동시출현간손상자（분별위4、2、2례）균사망。결론길비체니／액락체니치ILD적중위시간위24 d（1~210 d），주요림상표현위호흡곤난、해수、발열，용약7 d내출현ILD、유폐섬유화화방사성폐염병기왕사자、동시출현간손상자예후불가。본결론원우개안보도，유일정국한성。
Objective To explore the clinical characteristics and prognosis in patients with interstitial lung disease( ILD ) induced by gefitinib or erlotinib. Methods "Epidermal growth factor receptor tyrosine kinase inhibitors" "gefitinib" "erlotinib" "interstitial lung disease" "case report",and corresponding Chinese vocabularies were selected as key words and PubMed,MEDLINE,Web of Science, CNKI,Wanfang databases,VIP and CBMdisc from January 2001 to April 2014 were searched. The case reports of ILD induced by gefitinib or erlotinib were collected,the patients' age,sex,pathologic diagnosis and staging,anamnesis,history of treatment,ILD occurrence time,clinical manifestations,treatments and outcome were recorded. Results A total of 40 reports involving 60 patients were entered. Fifty-nine cases were diagnosed as non-small cell lung cancer. Thirty-five( 58. 3%) patients were treated with gefitinib,34 of them were given 250mg/d and one was given 500 mg/d. Twenty-five(41. 7%)cases were treated with erlotinib 150 mg/d. The shortest occurrence time of ILD was one day after medication,the longest time was 210 days after medication. Thirty-three(55. 0%)patients developed ILD during 7-28 days after medication. The major clinical manifestations of ILD due to gefitinib and erlotinib were dyspnea,cough and fever. Ten(16. 7%),2(3. 3%)and 2(3. 3%)cases developed erythra,diarrhea and liver injury at the same time,respectively. The patients who were diagnosed as ILD were withdrawn immediately and treated with symptomatic and harmonic therapy. Thirty patientsˊclinical symptom and imaging features were improved 3-90 days( median 10 days)later. Thirty patients died 1-80 days( median 6 days)later. The <br> patients who were diagnosed as ILD in less than 7 days after medication,had history of pulmonary fibrosis or radiation pneumonitis,and developed liver injury meanwhile(4,2,2,respectively)died. Conclusions The median time of ILD induced by gefitinib or erlotinib was 24 days( 1-210 days ). The major clinical manifestations of ILD were dyspnea,cough and fever. The prognosis was poor in patients who were diagnosed as ILD within 7 days after medication,had history of pulmonary fibrosis or radiation pneumonitis,and developed liver injury meanwhile.