靶向联合化疗与常规化疗治疗表皮生长因子受体基因突变肺腺癌患者的临床效果
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摘要
目的探讨靶向联合化疗治疗表皮生长因子受体(EGFR)基因突变晚期肺腺癌患者的临床疗效及靶向联合化疗对EGFR基因不同突变位点患者的疗效差别。方法选择安徽省胸科医院2016年1～12月收治确诊的64例EGFR基因检测阳性的Ⅲb/Ⅳ期肺腺癌患者,使用随机数字表方法分为靶向联合化疗组(33例)与常规化疗组(31例),同时对靶向联合化疗组患者按照其基因突变位点不同分为3个亚组(19外显子突变组、21外显子突变组、20外显子突变组)。靶向联合化疗组患者采用EGFR受体酪氨酸抑制剂靶向治疗联合培美曲塞+卡铂/顺铂治疗,常规化疗组患者采用培美曲塞+卡铂/顺铂治疗。比较两治疗组患者的近期及远期疗效,并对靶向联合化疗组不同位点远期疗效进行数据分析。结果靶向联合化疗组的中位无进展生存期高于常规化疗组,两组差异有统计学意义(P <0. 05),两组患者总体疗效和不良反应总发生率相似,差异无统计学意义(P> 0. 05)。靶向联合化疗组中,不同外显子突变的肺腺癌患者之间靶向联合化疗的生存期相似,差异无统计学意义(P> 0. 05)。结论 EGFR基因突变晚期肺腺癌患者接受靶向联合化疗能延长无进展生存时间,且不良反应未见增加。不同位点基因突变患者接受靶向联合化疗的临床效果无明显差别。
Objective To explore the clinical efficacy of combined target and chemotherapy in patients with advanced lung adenocarcinoma with EGFR gene mutation and the difference of treatment responses in patients with different singular EGFR mutations. Methods Sixty-four patients with stage Ⅲb/Ⅳ lung adenocarcinoma who had a single mutated EGFR expression were enrolled in this study between January 2016 and December 2016. They were randomized into combined target-and chemo-therapy group( n = 33) and the conventional chemotherapy group( n = 31) using the digital table method. Patients in combined therapy group were treated with EGFR-TKI combined with pemetrexed plus carboplatin/cisplatin. The conventional chemotherapy group received pemetrexed + carboplatin/cisplatin regime. The short-term and long-term survivals were compared between the two groups. At the same time,subgroup analysis was performed on patients with combined target and chemotherapy according to their gene mutation sites. Results The median progression-free survival in combined chemotherapy group was higher than that in conventional chemotherapy group( P < 0. 05). There was no significant difference in the overall efficacy between the two groups( P > 0. 05). The total incidence of adverse reactions was similar between the two groups( P > 0. 05). In subgroup analysis,the efficacy of targeted combination chemotherapy was similar among lung adenocarcinoma patients with different exon mutations( P > 0. 05). Conclusions Combination of targeted and chemotherapy for patients with advanced lung adenocarcinoma with singular EGFR mutation can prolong the progression-free survival without considerable adverse reactions. Thereis no difference in clinical effects of patients with different loci gene mutations in the targeted combination chemotherapy group.
Objective To explore the clinical efficacy of combined target and chemotherapy in patients with advanced lung adenocarcinoma with EGFR gene mutation and the difference of treatment responses in patients with different singular EGFR mutations. Methods Sixty-four patients with stage Ⅲb/Ⅳ lung adenocarcinoma who had a single mutated EGFR expression were enrolled in this study between January 2016 and December 2016. They were randomized into combined target-and chemo-therapy group( n = 33) and the conventional chemotherapy group( n = 31) using the digital table method. Patients in combined therapy group were treated with EGFR-TKI combined with pemetrexed plus carboplatin/cisplatin. The conventional chemotherapy group received pemetrexed + carboplatin/cisplatin regime. The short-term and long-term survivals were compared between the two groups. At the same time,subgroup analysis was performed on patients with combined target and chemotherapy according to their gene mutation sites. Results The median progression-free survival in combined chemotherapy group was higher than that in conventional chemotherapy group( P < 0. 05). There was no significant difference in the overall efficacy between the two groups( P > 0. 05). The total incidence of adverse reactions was similar between the two groups( P > 0. 05). In subgroup analysis,the efficacy of targeted combination chemotherapy was similar among lung adenocarcinoma patients with different exon mutations( P > 0. 05). Conclusions Combination of targeted and chemotherapy for patients with advanced lung adenocarcinoma with singular EGFR mutation can prolong the progression-free survival without considerable adverse reactions. Thereis no difference in clinical effects of patients with different loci gene mutations in the targeted combination chemotherapy group.
引文
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[12]张爽,柳影,程颖,等.中国不同表皮生长因子受体敏感突变类型非小细胞肺癌患者接受表皮生长因子受体酪氨酸激酶抑制剂一线治疗的临床疗效比较[J].中华肿瘤杂志,2016,38(3):211-217.
[2]李铁英,李华,战涛.不可逆性泛HER抑制剂HM781-36B在埃罗替尼耐药型非小细胞肺癌中的抗肿瘤活性[J].安徽医学,2016,38(1):29-32.
[3]GOLDSTRAW P.The 7th edition of TNM in lung cancer:what now?[J].J Thorac Oncol,2009,4(6):671-673.
[4]OKEN M M,CREECH R H,TORMEY D C,et al.Toxicity and response criteria of the Eastern Cooperative Oncology Group[J].Am J Clin Oncol,1982,5(6):649-656.
[5]EISENHAUER E A,THERASSE P,BOGAERTS J,et al.New response evaluation criteria in solid tumors:revised RE-CIST guideline(version 1.1)[J].Eur J Cancer,2009,45(2):228-247.
[6]ASAMI K,KOIZUMI T,HIRAI K,et al.Gefitinib as firstline treatment in eldly epidermal growth factor receptor-mutated patients with advanced lung adenocarcinoma:results of a nagano lung cancer research group study[J].Clin Lung Cancer,2011,12(6):387-392.
[7]KATO T,YOSHIOKA,OKAMOTO L,et al.Afatinib versus cisplatin plus pemetrexed in Japanese patients with advanced non-small cell lung cancer harboring activating\r,EGFR\r,mutations:subgroup analysis of LUX-Lung 3[J].Can Sci,2015,106(9):1202-1211.
[8]WU Y L,ZHOU C,CHENG Y,et al.Erlotinib as secondline treatment in patients with advanced non-small-cell lung cancer and asymptomatic brain metastases:a phase II study(CTONG.0803)[J].Ann Oncol,2013,24(4):993-999.
[9]周炜,张洁,贾海霞,等.EGFR不同突变亚型与肺腺癌脑转移预后的相关性分析[J].中华放射肿瘤学杂志,2017,26(2):144-149.
[10]GRIDELLI C,DEMARINIS F,DIMAIO M,et al.Gefitinib as first-line treatment for patients with advanced nonsmall-lung cancer with activating epidermal growth factor receptor mutation:review of the evidence[J].Lung Cancer,2011,71(3):249-257.
[11]ELLIS P M,COAKLEY N,FELD R,et al.Use of the epidermal growth factor receptor inhibitors gefitinib,erlotinib,afatinib,dacomitinib,and icotinib in the treatment of nonsmall-lung cancer:a systematic review[J].Cur Oncol,2015,22(3):183-215.
[12]张爽,柳影,程颖,等.中国不同表皮生长因子受体敏感突变类型非小细胞肺癌患者接受表皮生长因子受体酪氨酸激酶抑制剂一线治疗的临床疗效比较[J].中华肿瘤杂志,2016,38(3):211-217.