含铂方案联合西乐葆一线治疗晚期非小细胞肺癌的Ⅱ期临床研究

A phase Ⅱ clinical trial of celecoxib combined with platinum-based chemotherapy in the treatment of patients with advanced NSCLC as first-line treatment

背景与目的目前铂类联合第三代化疗药物的方案为晚期非小细胞肺癌的一线治疗方案,但其对中位生存期及1年生存率的改善已达平台期。本研究的目的是探讨含铂方案联合西乐葆一线治疗晚期非小细胞肺癌的疗效、影响因素及不良反应。方法选择免疫组化证实为COX-2阳性的初治晚期非小细胞肺癌患者接受铂类为基础的二联化疗方案(GP方案:吉西他滨1250mg/m2,d1、8+顺铂80mg/m2,分d1、d2给药;NP方案:长春瑞滨25mg/m2,d1、8+顺铂80mg/m2,分d1、d2给药;TP方案:多西紫杉醇75mg/m2,d1+顺铂80mg/m2,分d1、d2给药),同时在化疗开始前5-7天开始口服西乐葆400mg,Bid,直至病情进展或出现不可耐受的副反应。不良反应采用NCI-CTC标准。采用Kaplan-Meier法估计生存,Cox模型分析影响因素。评价终点:中位生存期、1年生存率、无疾病进展生存期、有效率及不良反应。结果2005年2月至2007年3月入组患者可评价者共44例,有效率为45%,疾病控制率为59%。中位无疾病进展生存期为6个月(95%CI:4-8个月),中位生存期为18个月(95%CI:9-27个月),1年生存率为68%。一线周期数和总体评效是影响PFS的预测因素,未发现明确影响生存期的预测因素。白细胞减少和恶心/呕吐为最常见的不良反应,发生率分别为59%和50%,Ⅲ/Ⅳ度不良反应占15%。结论西乐葆联合铂类为基础的化疗作为COX-2筛选阳性的晚期非小细胞肺癌患者一线治疗是有效的,而且毒副反应可以接受。

Background and objective Currently, platinum-based regimes are standard first-line chemotherapy for non-small cell lung cancer. The aim of this study is to evaluate the efficacy, influencing factors and adverse events of celecoxib plus platinum-based chemotherapy in advanced non-small cell lung cancer as first-line treatment. Methods Previously untreated patients of advanced non,small cell lung cancer with COX-2 positive, confirmed by immunohistochemical staining, were randomized to receive GP, NP or TP regimens. Celecoxib of 400 mg Bid was given, po 5-7 days before chemotherapy,and not stopped until evidence of disease progression or toxicity. Adverse events were cirtified according to NCI-CTC criteria. Kaplan-Meier method was used to analyze the survival rate. COX regression was used to define the predictive factors. Primary endpoint： median survival time, 1-year survival rate and median progression free survival time. Secondary endpoint： response rate and toxicity. Results Forty-four evaluable patients were enrolled in the study from February 2005 to March 2007. Response rate was 45%, disease control rate 59%. Median progression free survival time and median survival time were 6months （95%CI： 4-8 months） and 18 months （95%CI： 9-27months）, respectively. One-year survival rate was 68%. Numbers of chemotherapy cycles and overall evaluation were the predictive factors for PFS in COX model （P=0.023 and 0.000）. No factor was defined to affect survival time. Neutropenia and nausea/ vomit were the most common toxicity. Conclusion Celecoxib combined with platinum-based chemotherapy appears to be well tolerated and demonstrates encouraging activity in patients of previously untreated advanced NSCLC.