摘要
目的：探讨经不同二线方案治疗后晚期非小细胞肺癌（ NSCLC）患者的预后及其影响因素，分析患者的最适二线治疗方案。方法回顾性分析178例晚期NSCLC患者的临床资料，按二线治疗方案分为单药组（46例）、单药联合重组人血管内皮抑素（恩度）组（42例）和以铂类为基础的双药组（90例）。采用Kaplan-Meier法和Log rank检验进行生存分析，采用Cox比例风险模型进行预后影响因素的多因素分析。结果单药组、单药联合恩度组和双药组患者的中位无进展生存时间（PFS）分别为50、54和79 d，双药组患者的PFS高于单药组（P＝0．011）。单药组、单药联合恩度组和双药组患者的疾病控制率（ DCR）分别为26．1％、47．6％和46．7％，单药联合恩度组患者的DCR高于单药组（P＝0．041），双药组患者的DCR高于单药组（P＝0．016）。单药组、单药联合恩度组和双药组患者的有效率分别为2．2％、0和4．4％，差异无统计学意义（ P＞0．05）。 Cox多因素分析结果显示，二线基线TNM分期、二线基线神经元特异性烯醇化酶（ NSE）水平，一线开始至二线开始治疗时间、二线治疗周期数和治疗后疾病控制情况为影响二线治疗患者PFS的独立因素（均P＜0．05）。在年龄＜60岁、二线基线美国东部肿瘤协作组评分为0～1分、二线基线TNM分期为Ⅳ期、一线紫杉醇＋铂类方案、一线化疗周期数≤4个、一线开始至二线开始治疗时间3～6个月、一线疗效为稳定＋完全缓解＋部分缓解和二线治疗后Ⅰ度白细胞下降的患者中，双药组患者的中位PFS均高于单药组（均P＜0．05）；在一线开始至二线治疗开始时间3～6个月的患者中，单药联合恩度组患者的中位 PFS 高于单药组（ P＜0．05）。结论一线开始至二线开始治疗时间、二线基线TNM分期、NSE水平、二线治疗周期数和治疗后疾病控制情况为影响二线治疗患者PFS的独立因素。以铂类为基础的双药方案与标准单药方案比较，能提高二线治疗后患者的PFS和DCR，单药联合恩度方案疗效居中，单药化疗较差。
Objective The purpose of this study is to explore the efficacy and predictors of second-line chemotherpy in advanced non-small cell lung cancer patients and suggest optimal protocols suitable for differently characterized patients. Methods The clinical data of 178 advanced NSCLC patients second-line-treated in Tianjin Cancer Hospital from 2009.1.1 to 2013.12.31 were retrospectively analyzed. According to the different second-line treatments, the patients were divided into standard mono-drug therapy group （ 46 cases）, endostar combined with standard mono-drug therapy group （42 cases）, and platinum-based doublet chemotherapy group （ 90 cases） . Kaplan-Meier and Log-rank analyses were used to estimate and compare the＆amp;nbsp;survival rates in the groups, and Cox′s hazard regression model was used to determine the prognostic factors. Chi-square test was used to analyze the differences among different groups. Results The median progression-free survivals （ mPFS） were 50 days, 54 days, and 79 days （ P=0.042） for the standard mono-drug therapy group, endostar combined with standard mono-drug therapy group, and platinum-based doublet chemotherapy group, respectively. The differences between the mono-drug therapy group and doublet chemotherapy group were statistically significant （ P=0. 011 ） . The disease control rate （ DCR ） for each group was 26.1%, 47.6% and 46.7% （P=0.041）, and the DCR were statistically significantly different between the mono-drug therapy group and doublet chemotherapy group （ P=0.016） , and between the mono-drug therapy group and endostar combined with standard mono-drug therapy group （P=0.041）. The overall response rate （ORR） for each group was 2.2%, 0, and 4.4% （P〉0.05 for all）. Multivariate analysis showed that the period from the begining of first-line to second-line chemotherapy （ progression-free time） , base-line clinical stage, neuron specific enolase （ NSE） before second-line therapy, the cycles of second-line chemotherapy and the response to second-line therapy were independent predictors for PFS （ P〈0. 005 for all） . Subgroup analysis indicated that the patients obtained more clinical benefit from doublet chemotherapy rather than mono-drug therapy, with following factors： age〈60 years, paclitaxel plus cisplatin for first-line treatment, chemotherapy cycles≤4, CR, PR and SD for response, progression time within 3-6 months from the begining of first-line to second-line chemotherapy, performance status score≤1 at the begining of second-line therapy,Ⅳ stage, and mild leukopenia （ P〈0.05 for all） . The patients whose progression-free survival time within 3-6 months from the begining of the first-line to second-line chemotherapy got more clinical benefit from endostar combined with standard mono-drug chemotherapy than mono-drug therapy （ P=0.006） . Conclusions The period from the begining of first-line to second-line chemotherapy, base-line TNM stage, NSE before second-line chemotherapy, the cycles of second-line chemotherapy and the response to second-line therapy were independent predictors for PFS. Platinum-based doublet chemotherapy and endostar plus standard second-line regimen can improve the efficacy in some characterized advanced NSCLC as compared with the patients by standard mono-drug therapy, wherein the platinum-based chemotherapy revealed the best efficacy.
出处
《中华肿瘤杂志》
CAS
CSCD
北大核心
2016年第4期294-299,共6页
Chinese Journal of Oncology
基金
国家科技重大专项（2013ZX）
天津市科技计划（12ZCDZSY15600）
国家自然科学基金（81372517）
关键词
癌
非小细胞肺
抗肿瘤联合化疗方案
预后
Carcinoma,non-small-cell lung
Antineoplastic combined chemotherapy protocols
Prognosis
