目的 从miR-204-5p、miR-1269表达变化方面观察埃克替尼联合TP化疗治疗晚期非小细胞肺癌（NSCLC）的临床有效性和安全性。方法 前瞻性选取2019年2月—2020年12月河北北方学院附属第一医院胸外科NSCLC患者82例，计算机随机数字生成法分为对照组（n＝41）、试验组（n＝41）。对照组给予TP化疗，紫杉醇剂量175 mg·m^-2，第1天静脉滴注；卡铂剂量300 mg·m^-2，第2天静脉滴注。4周为1个周期，治疗4个周期。试验组在对照组TP方案治疗基础上加用埃克替尼，TP化疗方案及操作同对照组，同时口服埃克替尼，每次125 mg，每天3次，当患者出现3级及以上不良反应时，可暂停（1～2周）服用，待症状缓解或消失再次恢复每次125 mg，每天3次。4周为1个周期，治疗4个周期后进行效果评价。比较两组临床疗效、不良反应发生情况，分别于治疗前、治疗2个周期、治疗4个周期检测两组患者肺功能［第1秒呼气容积（FEV₁）、最大呼气容积（FVC）］、肿瘤标志物［糖类抗原125（CAl25）、癌胚抗原（CEA）、细胞角蛋白19片段（CYFRA21-1）］、miR-204-5p、miR-1269水平。结果 治疗4个周期后，试验组客观缓解率（ORR）为43.90%，疾病控制率（DCR）为82.93%，分别高于对照组的24.39%、63.41%（P<0.05）；治疗前两组患者FEV₁、FVC比较，差异无统计学意义（P>0.05）；治疗2个周期、4个周期后两组FEV₁、FVC均较治疗前升高，且同时间点试验组高于对照组（P<0.05）。治疗前两组患者CA125、CEA、CYFRA21-1比较，差异无统计学意义（P>0.05）；治疗2个周期、4个周期后两组CA125、CEA、CYFRA21-1较治疗前降低，且同时间点试验组低于对照组（P<0.05）；治疗前两组患者miR-204-5p、miR-1269表达水平比较，差异无统计学意义（P>0.05）；治疗2个周期、4个周期后两组miR-204-5p较治疗前升高，miR-1269较治疗前降低，且同时间点试验组miR-204-5p高于对照组，miR-1269低于对照组（P<0.05）。两组不良反应发生率比较，差异无统计学意义（P>0.05）。结论 埃克替尼联合TP化疗治疗晚期NSCLC效果显著，可有效改善患者肺功能，降低肿瘤标志物水平，调节miR-204-5p、miR-1269表达，且安全性高。

Objective To analyze the effect of icotinib combined with TP chemotherapy in treatment of advanced non-small cell lung cancer (NSCLC) from the expression changes of miR-204-5p and miR-1269 on the basis of previous studies. Methods A total of 82 NSCLC patients in Department of Thoracic Surgery, The First Affiliated Hospital of Hebei North University from February 2019 to December 2020 were prospectively selected. They were divided into control group (n=41) and experimental group (n=41) by computer random number generation method. Patients in the control group were given TP chemotherapy (paclitaxel + carboplatin), paclitaxel dose 175 mg·m^-2, intravenous drip on the first day, carboplatin dose 300 mg·m^-2, intravenous drip on the second day. Four weeks was one cycle, and four cycles of treatment. Patients in the experimental group were given icotinib on the basis of the TP regimen of the control group. The TP chemotherapy regimen and operation were the same as those of the control group. At the same time, icotinib was taken orally, 125 mg each time, three times a day. When patients had grade three or above adverse reactions, they stoped taking (1-2 weeks) and resumed taking 125 mg each time, three times a day, when the symptoms are relieved or disappeared. Four weeks was one cycle, and the effect was evaluated after four cycles of treatment. The clinical efficacy and adverse reactions of two groups were compared. The levels of lung function[first second expiratory volume (FEV₁), maximum expiratory volume (FVC)], tumor markers[carbohydrate antigen 125 (CA25), carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1)], miR-204-5p and miR-1269 were measured before treatment, two treatment cycles and four treatment cycles respectively. Results After four cycles of treatment, the objective remission rate (ORR) and disease control rate (DCR) of the experimental group were 43.90% and 82.93%, respectively higher than those of the control group (24.39% and 63.41%, P<0.05). There was no significant difference in FEV₁ and FVC between the two groups before treatment (P > 0.05). After two and four cycles of treatment, FEV₁ and FVC in the two groups were higher than those before treatment, and higher than those in the control group at the same time point (P<0.05). There was no significant difference in CA125, CEA and CYFRA21-1 between the two groups before treatment (P > 0.05). After two and four cycles of treatment, CA125, CEA and CYFRA21-1 in the two groups were lower than those before treatment, and at the same time, the levels of CA125, CEA and CYFRA21-1 in the experimental group were lower than those in the control group (P<0.05). There was no significant difference in the expression of miR-204-5p and miR-1269 between the two groups before treatment (P > 0.05). After two and four cycles of treatment, miR-204-5p increased and miR-1269 decreased in the two groups. At the same time, miR-204-5p in the experimental group was higher than that in the control group, and miR-1269 was lower than that in the control group (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P > 0.05). Conclusion Icotinib combined with TP chemotherapy is effective in treatment of advanced NSCLC. It can effectively improve lung function, reduce the level of tumor markers, regulate the expression of miR-204-5p and miR-1269, and has high safety.

R979.1

河北省医学科学研究课题（20211359）；张家口市市级科技计划（2021072D）