培美曲塞单药或联合吉非替尼治疗EGFR-TKI耐药后晚期非小细胞肺癌临床观察

背景与目的:生长因子受体-酪氨酸激酶抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitor,EGFR-TKI)治疗晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)获得性耐药后尚无标准的治疗方案,亟待探寻有效的后续治疗方法.为临床应用提供指导,该研究旨在比较后续治疗采用培美曲塞单药或联合吉非替尼治疗EGFR-TKI获得性耐药的晚期NSCLC的临床疗效及安全性.方法:入组既往接受过EGFR-TKI治疗后进展的晚期NSCLC患者62例.其中32接受培美曲塞联合吉非替尼治疗,设为联合组;30例单用培美曲塞治疗,设为化疗组.评价临床疗效及不良反应.结果:联合组客观有效率(objective response rate,ORR)为46.9%,高于化疗组的20%,差异有统计学意义(χ2=4.933,P<0.05);两组疾病控制率(disease control rate,DCR)差异无统计学意义(P>0.05);联合组的中位无病生存期(progression-free survival,PFS)为8.0个月,化疗组中位PFS为6.3个月,差异有统计学意义(χ2=8.063,P<0.05),两组总生存期(overall survival,OS)差异无统计学意义(P>0.05).联合组中性粒细胞减少、皮疹的发生率高于化疗组,差异有统计学意义(P<0.05),Ⅲ~Ⅳ不良反应两组差异无统计学意义(P>0.05).结论:晚期NSCLC患者EGFR-TKI获得性耐药后,采用培美曲塞联合吉非替尼较单用培美曲塞显示出更优势临床有效率和中位PFS,不良反应可耐受,值得临床推广运用.

Pemetrexed with geiftinib or pemetrexed alone in advanced non-small cell lung cancer with acquired resistance to EGFR tyrosine kinase inhibitors

Background and purpose:New treatment methods should be explored for non-small cell lung cancer (NSCLC) patients with acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). This study compared the curative effect of pemetrexed with geiftinib or pemetrexed alone in advanced NSCLC with acquired resistance to EGFR-TKI.Methods:This study included 62 NSCLC patients with advanced EGFRgene mutation and acquired resistance to EGFR-TKI. Among those, 32 patients were treated with pemetrexed and geiftinib, and 30 patients treated with geiftinib alone. The differences in outcomes between the two strategies were assessed.Results:Objective response rate (ORR) was 46.9% for those treated with pemetrexed and geiftinib and 20%for those treated with pemetrexed alone(χ2=4.933,P<0.05). There was no signiifcant differences between the two groups on disease control rate (DCR) (P>0.05). The median progression-free survival (PFS) was 8.0 months on pemetrexed and gefitinib group and 6.3 months on pemetrexed alone (χ2=8.063,P<0.05). There was no significant differences between the two groups on overall survival (OS) (P>0.05). Higher occurrence of leukocytopenia and rash was observed in the pemetrexed and geiftinib group than in the pemetrexed group (P<0.05). There was no signiifcant differences be-tween the two groups on grade 3-4 toxicities (P>0.05).Conclusion:This study was to demonstrate that continuation of EGFR-TKI with pemetrexed in patients with acquired resistance improves outcomes compared with pemetrexed alone. An improved response rate and PFS were observed in this study. A larger prospective clinical trial is needed to further evaluate this promising strategy.