含顺铂的三组联合化疗方案治疗晚期非小细胞肺癌的随机对照临床研究

A Randomized Comparative Trial of Three Combined Regimens Containing Cisplatin for Treatment of Advanced Non-Small Cell Lung Cancer

背景与目的:长春瑞滨(vinorelbine,NVB)、紫杉醇(paclitaxel,TAX)和吉西他滨(gemcitabine,GEM)是目前治疗肺癌的一线药物,它们分别与顺铂(cisplatin,DDP)联合治疗晚期非小细胞肺癌(non-smallcelllungcancer,NSCLC)疗效确切。但是关于三种联合化疗方案疗效及不良反应的比较,目前国内多为回顾性研究。本研究对这三组含DDP的联合化疗方案治疗晚期NSCLC的近期疗效及不良反应进行对比,为临床选择合适的化疗方案提供参考。方法:采用前瞻性开放性随机对照临床研究方法,对276例入组患者随机采用NP(NVB、DDP)、TP(TAX、DDP)或GP(GEM、DDP)方案化疗,化疗至少2周期后评价疗效及不良反应,进行组间比较。结果:NP组、TP组、GP组有效率分别是42.3%(41/97)、43.0%(40/93)和43.4%(36/83);CR率分别为1.0%(1/97),2.2%(1/93)和0(0/83);中位生存期分别为8.5、8.8、9.2个月;无病生存期分别为4.1、3.8、3.9个月;1年生存率分别为31.9%、33.3%和31.3%;各组间差异均无显著性。主要不良反应是Ⅲ～Ⅳ度骨髓抑制、恶心呕吐、乏力和静脉炎。GP组的白细胞减少(42.2%)、中性粒细胞减少(36.2%)发生率最低,血小板减少发生率(53.0%)最高,与NP组(77.8%、67.7%、12.1%)、TP组(71.0%、57.0%、13.0%)比较差异均具有显著性(P<0.01);GP组、TP组的恶心呕吐发生率分别为16.8%、25.8%,均显著低于NP组(41.4%)(P=0.000,0.022)。GP组的乏力症状发生率(38.5%)、NP组的静脉炎发生率(58.6%)显著高于其他两组(P<0.01)。结论:TP、NP和GP方案治疗晚期NSCLC近期疗效差异无显著性。NP方案不良反应较多,患者耐受性相对较差;TP、GP方案耐受性较好并各有优势。

BACKGROUND ＆ OBJECTIVE： Vinorelbine （NVB）, paclitaxel （TAX）, and gemcitabine （GEM） are first-line chemotherapeutic drugs in the treatment for non-small cell lung cancer （NSCLC） currently. There are many domestically retrospective studies to compare efficacies and adverse reactions among these three regimens, all of which has composed of cisplatin （DDP）. This randomized study was to investigate the efficacies and toxicities of these three regimens in NSCLC treatment, in order to choose a feasible regimen for NSCLC patients. METHODS： A total of 276 NSCLC patients were randomly assigned to a regimen of NP （NVB plus DDP ）, or TP （TAX plus DDP） , or GP （GEM plus DDP）. Efficacies and toxicities were analyzed and compared after two cycles. RESULTS： The response rates were 42.3% （41/97） in NP arm, 43.0% （40/93） in TP arm, and 43.4% （36/83） in GP arm, and complete remission rates were 1.0% （1/97）,2.2% （1/93） and （0/83） respectively, without significant difference. The median survival time, diseasefree survival time and 1-year survival rate were 8.5 months, 4.1 months and 31.9%; 8.8 months, 3.8 months and 33.3%, and 9.2 months, 3.9 months, 31.3%, respectively in NP, TP and GP arms without significant difference. The major adverse reactions were stage 3 to 4 myelo-suppression, nausea/vomiting, fatigue and phlebitis. There were highest incidences of leucopenia （42.2%）, neutropenia （36.2%） and lowest incidence of thrombocytopenia （53.0%） in GP arm compared to NP arm （77.8%,67.7%,12.1%） or TP arm （71.0%,57.0%,13.0%） statistically （P〈0.01 for all）. The rates of nausea/vomiting in GP arm （16.8%） and TP arm （25.8%） were significantly lower than in NP arm （41.4%）（P〈0.05） ; and the rate of fatigue in GP arm （38.5%） or phlebitis in NP arm was most frequent among the three arms （P=0.000, 0.008 respectively）. CONCLUSIONS： There is no significant difference in short-term efficacy of chemotherapy regimen NP, TP and GP. TP and GP regimens, both of which possesses its own advantage, are more tolerable than NP regimen which has the most side effects.