培美曲塞联合铂类药物一线治疗晚期非小细胞肺癌的疗效及预测因素分析

Abstract

目的 研究培美曲塞联合铂类药物一线用药治疗晚期非小细胞肺癌(NSCLC)的近期及远期疗效,分析胸苷酸合酶(TS)表达与培美曲塞联合铂类药物疗效的关系.方法 回顾性分析2008年1月至2009年10月在北京肿瘤医院接受培美曲塞联合铂类药物一线化疗的51例Ⅲb/Ⅳ期非鳞癌NSCLC患者.共35例患者接受培美曲塞联合顺铂方案化疗,16例接受培美曲塞联合卡铂方案化疗.对其中30例的组织标本采用免疫组织化学法检测TS的表达.主要研究终点为总生存期,次要终点为缓解率、无进展生存期及不良反应.采用SPSS 16.0软件进行统计学分析.运用卡方检验分析临床因素等与化疗疗效的相关性,采用Kaplan-Merier曲线法和log-rank检验进行生存分析.结果 51例患者中1例失访(但可评价疗效及无进展生存期),余50例资料完整.客观有效率(完全缓解+部分缓解)为37％(19/51),疾病控制率(完全缓解+部分缓解+稳定)为71％ (36/51).中位无进展生存(PFS)为5.3个月(95％ CI为3.9 ～6.7),中位总生存期为19.0个月(95％ CI为11.6～26.4).单因素分析结果显示,性别、病理类型、吸烟状态和疗效与生存期相关.多因素分析结果显示,病理类型是影响患者总生存期的独立预后因素.根据美国国立癌症研究所常见毒性分级标准,3～4级不良反应的发生率低,主要包括白细胞减少(5/51)、中性粒细胞减少(10/51)及消化道反应(2/51).30例患者的标本中TS表达阳性10例.卡方分析结果显示,TS表达与疗效无关.多因素分析结果显示,病理类型、疗效及TS表达水平与总生存期相关(均P＜0.01).结论 培美曲塞联合铂类药物一线用药治疗晚期非鳞癌NSCLC疗效确切,患者耐受性好.TS表达水平与患者生存期相关.

Objective To evaluate the effect of pemetrexed plus platinum for chemotherapy-naive advanced non-small cell lung cancer (NSCLC),and to explore thymidylate synthetase (TS) expression as the predictive and prognostic factor for this treatment. Methods This retrospective study enrolled 51 patients with chemotherapy-naive advanced NSCLC (non-squamous) treated at Department of Thoracic Medical Oncology in Beijing Cancer Hospital from Jan 2008 to Oct 2009.All patients received pemetrexed plus platinum as first-line treatment. TS expression was detected in 30 patients who had enough tissue samples by immunohistochemistry. Results The objective response rate (ORR) was 37.3％. Median progression-free surrival (PFS) was 5.3 months (95％ CI:3.9 - 6.7 ),and median overall surrival (OS)was 19.0 months (95％ CI:11.6 - 26.4). Univariate analysis showed that gender,pathology,smoking status and response were significantly correlated with OS. Cox-regression analysis showed that pathology was an independent prognostic factor.Rate of Grade 3/4 adverse events was low.In 30 patients with enough tissue samples were available,TS expression positive rate was 33.3％ ( 10/30). Chi-square test showed that TS expression was not associated with ORR. Multivariate analysis showed that pathology,response and TS expression (P =0.003,0.005 and 0.001,respectively) were the prognostic factors.Conclusion The therapeutic effect and tolerance of pemetrexed plus platinum regiment were definite as first-line treatment for chemotherapy-naive advanced NSCLC,and TS expression was an independent prognostic factor.