吉非替尼对比培美曲塞联合顺铂治疗术后EGFR突变阳性Ⅱ～Ⅲ A期肺腺癌的临床分析  

Clinical analysis of gefitinib versus pemetrexed combined with cisplatin in patients with stage Ⅱ-Ⅲ Alung adenocarcinoma harbouring positive EGFR mutations

作　　者：谢厚耐 李猛[1] 许林 王晖[1] 彭岳[1] 彭忠民[1] XIE Hounai;LI Meng;XU Lin;WANG Hui;PENG Yue;PENG Zhongmin(Department of Thoracic Surgery,Shandong Provincial Hospital Affliated to Shandong University,Jinan 250021,Shandong,China)

机构地区：[1]山东大学附属省立医院胸外科,山东济南250021

出　　处：《山东大学学报（医学版）》2018年第9期29-34,共6页Journal of Shandong University:Health Sciences

基　　金：山东省科技发展计划(2012GSF11826)

摘　　要：目的对照分析吉非替尼与培美曲塞联合顺铂治疗术后Ⅱ~ⅢA期肺腺癌的临床疗效及安全性,为术后肺腺癌辅助治疗方案的选择提供参考。方法回顾性选取2013年1月至2017年4月术后病理分期为Ⅱ~ⅢA期并存在表皮生长因子受体(EGFR)突变阳性的103例肺腺癌患者,根据治疗方案,分为培美曲塞+顺铂(PC)组与吉非替尼(GE)组。所有事件均终止于疾病出现进展、患者死亡或出现难以耐受的不良反应。采用Kaplan-Meier法和COX回归分析评估影响患者生存的因素。结果 PC组与GE组的中位随访时间分别为32.3个月和37.0个月,PC组患者的中位无病生存期(DFS)为21.0个月,明显低于GE组34.9个月,差异有统计学意义(P=0.002);两组间总生存期(OS)差异无统计学意义(P=0.182)。PC组患者最常见的不良反应为中性粒细胞减少(58.8%)、恶心呕吐(56.9%)、贫血(45.1%);GE组最常见的不良反应为皮疹(76.9%)、转氨酶升高(48.1%)、腹泻(42.3%)。PC组患者血液学毒性(中性粒细胞减少等)、消化道毒性(恶心呕吐等)、秃头症的发生率明显高于GE组,差异有统计学意义(P=0.001;P<0.001;P=0.020);GE组1例患者在服用药物后的3个月确诊为间质性肺炎(ILD)。GE组患者3级以上不良反应的发生率低于PC组(13.5%vs 33.3%),差异有统计学意义(P=0.020)。结论对于术后Ⅱ~ⅢA期且存在EGFR突变阳性的肺腺癌患者,相对于培美曲塞联合顺铂辅助化疗,行吉非替尼治疗有更长的DFS及更轻微的不良反应,可作为术后辅助治疗的优先选择。Objective To compare the efficacy of geftinib versus pemetrexed/cisplatin in patients with EGFR-mutant stageⅡ-ⅢA lung adenocarcinoma,and to provide a reference for the therapy of postoperative lung adenocarcinoma. Methods A total of 103 patients with pathological stage Ⅱ-ⅢA lung adenocarcinoma combined with positive epidermal growth factor receptor（ EGFR） mutations were enrolled between January 2013 and April 2017,and divided into pemetrexed ＋cisplatin（ PC） group and gefitinib（ GE） group. All events continued untill disease relapse,death,or unacceptable toxic effects. Factors affecting survival were assessed by Kaplan-M eier method and Cox regression analysis. Results The me-dian follow-up time was 32. 3 months in PC group and 37. 0 months in GE group. M edian disease-free survival（ DFS）was significantly longer in GE group than that in PC group（34. 9 vs 21. 0 months,P = 0. 002）. Overall survival（ OS）was not significantly different between the two groups（ P = 0. 182）. The most common adverse events in PC group were neutropenia（58. 8%） followed by nausea or vomiting（56. 9%） and anemia（45. 1%）,and in GE group were rash（76. 9%）,aminotransferase elevation（48. 1%） and diarrhoea（42. 3%）. The incidence of hematological toxicity,gastrointestinal toxicity and alopecia in PC group was significantly higher than that in GE group（ P = 0. 001; P〈0. 001; P = 0. 020）. Interstitial lung disease（ ILD）,which was regarded as the most severe treatment-related adverse event,was diagnosed in one patient after receiving gefitinib three months. The incidence of sever adverse events（ grade≥3） was significantly lower in GE group than that in PC group（13. 5% vs 33. 3%,P = 0. 020）. Conclusion Compared with chemotherapy with pemetrexed/cisplain,gefitinib shows a significant DFS benefit in patients with EGFR mutation-positive and completely resected stage Ⅱ-ⅢA lung adenocarcinoma and is associated with more favourable tolerability. Adjuvant geftinib could be a

关 键 词：肺腺癌 表皮生长因子受体突变 吉非替尼 培美曲塞 辅助化疗 

分 类 号：R655.3[医药卫生—外科学]