化疗序贯靶向药物治疗表皮生长因子受体-酪氨酸激酶抑制剂获得性耐药老年晚期非小细胞肺癌患者临床研究

Clinical study of sequential targeted drug therapy following chemotherapy in treatment of elderly advanced non-small cell lung cancer patients with acquired epidermal growth factor receptor-tyrosine kinase inhibitor resistance

目的观察培美曲塞联合顺铂序贯表皮生长因子受体一酪氨酸激酶抑制剂（EGFR-TKI）治疗老年晚期EGFR-TKI获得性耐药非小细胞肺癌（NSCLC）患者的疗效及不良反应。方法回顾性分析青岛市中心医院2012年3月至2014年3月收治的97例老年晚期EGFR-TKI获得性耐药NSCLC患者的临床资料，患者按治疗方法分为两组，对照组单独采用化疗，包括：培美曲塞500mg／m^2，第1天；顺铂75mg／m^2，第1天至第3天。研究组在化疗后序贯EGFR-TKI（吉非替尼250mg／d或厄洛替尼150mg／d或埃克替尼375mg／d），比较两组患者疗效、不良反应及无进展生存时间。结果对照组和研究组患者的疾病控制率分别为41．67％（20／48）和6531％（32／49），差异有统计学意义（χ^2=5．448，P=0．020）；客观缓解率分别为16．67％（8／48）和28．57％（14／49），差异无统计学意义（χ^2=1．960，P：0．162）；中位无进展生存期分别为4．0个月（95％U3．554-4．446）和4．5个月（95％口3．902-5．098），差异有统计学意义（χ^2=3．936，P：0．047）；两组患者的不良反应差异无统计学意义（P〉0．05）。结论培美曲塞联合顺铂序贯EGFR-TKI适用于EGFR．TKI耐药老年晚期NSCLC患者的治疗。

Objective To evaluate the efficacy and adverse effects of sequential administration of epidermal growth factor reeeptor-tyrosine kinase inhibitor （EGFR-TKI） following pemetrexed combined with cisplatin in elderly advanced non-small cell lung cancer （NSCLC） patients with acquired EGFR-TKI resistance. Methods A total of 97 elderly patients with advanced NSCLC confirmed with pathology or cytology in Qingdao Center Hospital from March 2012 to March 2014 were devided into control group and research group according to treatment methods. The control group received pemetrexed 500 mg/m^2 day 1 and cisplatin 75 mg/m^2 day 1-3, and the research group received pemetrexed 500 mg/m^2 and eisplatin 75 mg/m^2, then received sequential administration of EGFR-TKI （gefitinib 250 mg/d or elotinib 150 mg/d or icotinib 375 rag/d）. The efficacy, progression-free survival （PFS） and toxicity in both groups were compared. Results The disease control rate of control group and research group were 41.67 % （20/48） and 65.31% （32/49）, the difference was statistica[ly significant χ^2 = 5.448, P = 0.020）. The objective response rate of control group and research group were 16.67 % （8/48） and 28.57 % （14/49）, the difference was not statistically significant χ^2 = 1.960, P = 0.162）. The median PFS time of control group and research group were 4.0 months （95 % CI 3.554-4.446） and 4.5 months （95 % CI 3.902-5.098）, the difference was statistically significant χ^2= 3.936, P = 0.047）. There was no significant difference in adverse reactions between the two groups （P 〉 0.05）. Conclusion The sequential administration of EGFR-TKI following pemetrexed combined with cisplatin is suitable for the treatment of elderly advanced NSCLC patients with acquired EGFR-TKI resistance.