培美曲塞单药或联合吉非替尼治疗EGFR-TKI耐药后晚期肺腺癌临床观察

发布时间：2018-06-05 14:16

本文选题：培美曲塞 + 吉非替尼　；参考：《郑州大学》2016年硕士论文

【摘要】：背景与目的表皮生长因子受体-酪氨酸激酶受体抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitor, EGFR-TKI)广泛应用于临床,疗效显著,被NCCN指南推荐用于伴EGFR突变阳性的非小细胞肺癌的一线治疗。但EGFR-TKI靶向治疗在中位8-16个月后不可避免的出现耐药进展,目前获得性耐药后的后续治疗方法尚无标准方案。为探求更优的后续治疗策略,本文选取EGFR-TKI最终获得性耐药的晚期肺腺癌患者,后续治疗采用培美曲塞或培美曲塞联合吉非替尼,比较两者临床疗效及安全性。方法1 入组我院2012年3月—2014年10月期间收治的伴EGFR突变阳性的晚期肺腺癌患者62例,既往一线行含铂双药化疗,接受EGFR-TKI一线维持或二线治疗后获得性耐药,病情缓慢进展。2随机分为联合组和化疗组,化疗组30例给予培美曲塞500mg/m2,静脉滴注,dl,每21天一个周期,直至肿瘤进展或不良反应无法耐受。联合组32例给予培美曲塞500mg/m2,静脉滴注,d1,每21天一个周期,吉非替尼250mg, qd,口服,直至肿瘤进展或不良反应无法耐受。3以客观有效率(objective response rate, ORR)、疾病控制率(disease control rate, DCR)、不良反应、无进展生存期(progression-free survival, PFS)、总生存期(overallsurvival, OS)为评价指标,比较两组间的差异。结果1近期疗效全部入组62例病例均完成2个周期化疗,可评价疗效。联合组ORR为63.3%,化疗组ORR为33.3%,联合组ORR高于化疗组,差异有统计学意义(χ=4.218,P=0.040),联合组DCR为84.4%,化疗组DCR为80.0%,差异无统计学意义(χ2=0.203,P=0.652)。2远期疗效从接受本次治疗第1日开始计算,随访时间截止至2015年7月。联合组的中位PFS为8.0月,化疗组中位PFS为6.3月,联合组中位PFS高于化疗组,差异有统计学意义(χ2=8.063,P=0.005),联合组中位OS为12.7月,化疗组中位OS为10.0月,差异无统计学意义(χ2=3.170,P=0.075)。3不良反应主要表现在血液系统毒性和胃肠道反应,1-2级多见,3-4级发生率低。与化疗组相比,联合组白细胞减少(χ2=4.089,P=0.043)、皮疹(χ2=5.858,P=0.027)发生率高。不良反应经对症处理缓解,未影响后续化疗。结论晚期肺腺癌患者EGFR-TKI获得性耐药后,后续治疗采用培美曲塞联合吉非替尼治疗较单用培美曲塞可获得更高的ORR,中位PFS延长,不良反应可耐受,结果尚需大样本资料验证。
[Abstract]:Background & objective Epidermal growth factor receptor-tyrosine kinase receptor inhibitor (EGFR-TKI) has been widely used in clinical practice. It is recommended by NCCN guidelines for first-line treatment of non-small cell lung cancer with EGFR mutation positive. However, the progress of drug resistance is inevitable after the median 8-16 months of EGFR-TKI targeted therapy, and there is no standard protocol for subsequent treatment after acquired drug resistance. In order to find a better strategy for follow-up treatment, we selected advanced lung adenocarcinoma patients with EGFR-TKI final acquired drug resistance. The patients were treated with pemetrexed or pemetrexil combined with gefitinib. The clinical efficacy and safety of the two methods were compared. Methods from March 2012 to October 2014, 62 cases of advanced lung adenocarcinoma with EGFR mutation positive were treated in our hospital. The patients were treated with chemotherapy containing platinum and acquired drug resistance after first-line maintenance or second-line EGFR-TKI therapy. The patients in the chemotherapy group were treated with pemetrexil 500 mg / m ~ (2), intravenous drip of dl every 21 days, until tumor progression or adverse reactions were intolerable. 32 patients in the combined group were given pemetrexide 500 mg / m2, intravenous drip for d 1 every 21 days, gifitinib 250 mg, QD, oral, until tumor progression or adverse reactions could not tolerate 3. 3 to achieve objective effective rate of objective response rate.orr, disease control rate.DCRs, adverse reactions. Progression-free survival, PFSs, total survival time over survival (OS) were used to evaluate the difference between the two groups. Results 1 two cycles of chemotherapy were completed in all 62 patients, and the curative effect could be evaluated. The ORR of the combined group was 63.3 and the ORR of the chemotherapy group was 33.3. The ORR of the combined group was higher than that of the chemotherapy group (蠂 ~ (4) 218), the DCR of the combined group was 84.4m, and the DCR of the chemotherapy group was 80.00.There was no significant difference (蠂 ~ (2 +) 0.20 ~ (3) P 0.6522.2. the long-term curative effect was calculated from the first day of the treatment. The follow-up period ended in July 2015. The median PFS of the combined group was 8.0 months and the median PFS of the chemotherapy group was 6.3 months. The median PFS of the combined group was higher than that of the chemotherapy group, and the difference was statistically significant (蠂 ~ 2 / 8.063P ~ + 0.005). The median OS of the combined group was 12.7 months, and the median OS of the chemotherapy group was 10.0 months. There was no significant difference between them (蠂 ~ 2 / 3.170) (蠂 ~ 2 = 3.170). The main adverse reactions were blood system toxicity and gastrointestinal reaction in grade 1-2. The incidence rate of grade 3-4 was lower than that of grade 1-2. Compared with the chemotherapy group, the incidence of leukopenia and rash in the combined group was higher than that in the chemotherapy group (蠂 2 / 4.089 / P = 0.043 / P, 蠂 ~ 2 = 5.858 / P = 0.027). The adverse reaction was alleviated by symptomatic treatment and did not affect the follow-up chemotherapy. Conclusion after acquired drug resistance (EGFR-TKI) in patients with advanced lung adenocarcinoma, pemetrexil combined with gefitinib can obtain higher ORR than pemetrexil alone. The median PFS is longer and the adverse reaction is tolerable. The results need to be verified by large sample data.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R734.2

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