多西他赛单药与多西他赛联合铂类方案二线治疗晚期非小细胞肺癌的比较

目的 比较晚期非小细胞肺癌(NSCLC)患者二线治疗中多西他赛单药与多西他赛联合铂类方案的疗效及毒副反应,为NSCLC的二线规范治疗提供依据.方法 回顾性分析2004年1月至2008年5月在上海交通大学附属胸科医院接受二线化疗的152例晚期NSCLC患者的临床资料.40例接受多西他赛单药治疗(单药组),其中Ⅲb期16例,Ⅳ期24例;治疗前体力状况(PS)评分0～1分32例,2分8例.112例接受多西他赛联合铂类治疗(联合组),其中Ⅲb期29例,Ⅳ期83例;治疗前PS评分0～1分98例,2分14例.主要研究终点为总生存期(OS),次要研究终点为疾病控制率(DCR)、无疾病进展时间(PFS)、1年生存率及药物毒副反应.应用Kaplan-Meire方法进行生存分析,并进行各影响因素与预后关系的单因素及多因素分析.结果 单药组中位PFS(3.0个月)短于联合组(4.2个月,P=0.048),中位OS(17.0个月)、DCR(61.1%)和1年生存率(84.6%)与联合组(18.8个月、69.1%、86.9%)比较,差异均无统计学意义(均P0.05).单药组Ⅲ～Ⅳ度白细胞减少和胃肠道反应发生率分别为32.5%和0,均明显低于联合组(56.2%,4.5%,均P=0.000).预后因素分析显示既往接受手术危险比(HR)=0.428,95%可信区间(CI)为0.261～0.701]、治疗前PS评分(HR=1.919,95% CI为0.999～3.685)、肿瘤分期(HR=2.297,95% CI为1.427～3.696)以及二线治疗获益(HR=0.318,95% CI为0.177～0.571)是NSCLC的独立预后因素.结论 多西他赛联合铂类方案二线治疗与多西他赛单药方案相比有助于延长一般情况较好的晚期NSCLC患者的无疾病进展时间,但未显著增加患者的总生存期,并可给患者带来更大的血液学及胃肠道毒性.

Comparison of single-agent docetaxel versus docetaxel plus platinum combination agent in secand-line treatment for advanced non-small cell lung cancer

Objective To compare the therapeutic efficacies and toxicities of single-agent docetaxel or docetaxel plus platinum combination agent in patients with advanced non-small cell lung cancer (NSCLC) so as to provide rationales for standard second-line chemotherapy. Methods The clinical data from 152 patients with NSCLC who were admitted into Chest Hospital Affiliated to Shanghai Jiantong University, from January 2004 to May 2008 were retrospectively analyzed. Forty patients were treated with single-agent docetaxel (single-agent group, 16 and 24 patients with stages Ⅲb and Ⅳ disease respectively; 32 patients with PS score 0-1 before treatment and 8 patients with PS score 2 before treatment), and 112 patients were treated with docetaxel plus platinum combination agent (combination group, 29 and 83 patients with stage Ⅲ b and Ⅳ disease respectively; 98 patients with PS score 0 - 1 before treatment and 14 patients with PS score 2 before treatment). Primary end point was overall survival (OS) ,and secondary end point were progression-free survival time (PFS), disease control rate (DCR), one-year survival, and drug toxicity. Survival analysis was evaluated by Kaplan-Meier. Single factor analysis and Cox regression model were done to analyze the relationship between the influencing factors and the prognosis of disease. Results The median PFS of the single-agent group was 3.0 months, significantly shorter than that of the combination gtoup (4.2 months, P=0.048). However, no statistical differences were found in OS, DCR or one-year survival between the two groups (all P0.05). The most common grade 3 to 4 toxicities were leukopenia (32.5% for single-agent group, and 56.2% for combination group, P=0.000), and gastro-intestinal toxicity (0 for single-agent group, and 4.5% for combination group, P=0.000). Single factor analysis showed that the factors including radiotherapeutic history, operative history, PS score before treatment, clinical stage, and response to second-line treatment influenced the prognosis of NSCLC (all P<0.05). Cox regression analysis demonstrated operative history(HR=0.428, 95% CI: 0.261-0.701), PS score before treatment (HR=1.919, 95% CI: 0.999-3.685), clinical stage (HR=2.297, 95% CI: 1.427-3.696) and response to second-line treatment (HR=0. 318, 95% CI: 0.177-0.571) had effects on survival. Conclusions To those well-selected patients, docetaxel plus platinum combination agent as the second-line treatment of advanced NSCLC significantly prolongs the progression-free survival. But such a regimen is more toxic and does not improve the response rate and overall survival.