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

doi:10.6040/j.issn.1671-7554.0.2018.419

摘要/Abstract

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。

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

Abstract: Objective To compare the efficacy of geftinib versus pemetrexed/cisplatin in patients with EGFR-mutant stage Ⅱ-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-Meier method and Cox regression analysis. 山东大学学报 (医学版)56卷9期 -谢厚耐,等.吉非替尼对比培美曲塞联合顺铂治疗术后EGFR突变阳性Ⅱ~ⅢA期肺腺癌的临床分析 \=- Results The median follow-up time was 32.3 months in PC group and 37.0 months in GE group. Median 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 potential treatment option compared with adjuvant chemotherapy in these patients.

Key words: Lung adenocarcinoma, Epidermal growth factor receptor mutation, Gefitinib, Pemetrexed, Adjuvant chemotherapy

中图分类号:

R655.3

谢厚耐,李猛,许林,王晖,彭岳,彭忠民. 吉非替尼对比培美曲塞联合顺铂治疗术后EGFR突变阳性Ⅱ~ⅢA期肺腺癌的临床分析[J]. 山东大学学报 (医学版), 2018, 56(9): 29-34.

XIE Hounai, LI Meng, XU Lin, WANG Hui, PENG Yue, PENG Zhongmin. Clinical analysis of gefitinib versus pemetrexed combined with cisplatin in patients with stage Ⅱ-ⅢA lung adenocarcinoma harbouring positive EGFR mutations[J]. Journal of Shandong University (Health Sciences), 2018, 56(9): 29-34.

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