血清DKK1水平在塞来昔布一线联合铂类化疗治疗晚期非小细胞肺癌随机对照研究中的临床意义  

Serum DKK-1 levels in the advanced non-small cell lung caner patients: a randomized clinical study on combination of celecoxib with cisplatin-based chemotherapy

作　　者：滕家俊[1] 裴俊[1] 韩宝惠[1] 姜丽岩[1] 钟华[1] 顾爱琴[1] 储天晴[1] 

机构地区：[1]上海交通大学附属胸科医院呼吸内科,上海200030

出　　处：《世界临床药物》2015年第6期388-393,共6页World Clinical Drug

基　　金：上海市胸科医院科技发展基金项目(YZ14-10);上海市胸科医院科技发展基金重大重点项目(2014YZDC10101);上海市自然科学基金项目(12ZR1428800);上海市科委基础重点项目(11JC1412200)

摘　　要：目的通过塞来昔布一线与铂类化疗联合治疗晚期非小细胞肺癌(NSCLC)的随机对照研究评价环氧合酶2(COX-2)抑制剂的抗肿瘤作用及安全性;通过治疗过程中血清DKK1的监测探讨COX-2抑制剂相关的作用机制及疗效预测因子。方法初治Ⅲ-Ⅳ期NSCLC患者81例,随机分为治疗(长春瑞滨/顺铂+塞来昔布)组及对照(长春瑞滨/顺铂)组。直至第4个疗程中和后随访病情进展。患者初次化疗前及化疗2个疗程后ELISA法检测血清DKK1水平。结果治疗组客观缓解率(ORR)为34.1%,对照组为15.0%,两组差异具有统计学意义(P<0.05),治疗组无进展生存期(PFS)略长,为6.3个月,对照组为5.9个月,但差异未达到统计学意义的显著性。治疗前两组患者血清DKK1水平均无差异,且分别与患者年龄、性别、病理分型、分期、吸烟状况和ECOG评分无统计学意义的相关性。化疗2个疗程后两组血清DKK1水平均呈现下降趋势,但治疗组血清DKK1的下降幅度明显大于对照组(中位降低值分别为37.58对2.83 pg/ml,P=0.01);治疗组治疗后血清DKK1水平明显低于治疗前(P<0.05),对照组治疗前后差异不明显。两组治疗前后血清DKK1水平均未发现与化疗疗效显著相关(P分别为0.908,0.730,0.515,0.413)。两组治疗前血清DKK1水平均未能与患者PFS呈现显著相关(P=0.090,0.890),但塞来昔布组化疗后血清DKK1的下降幅度与患者PFS显著相关(P=0.043)。结论 COX-2抑制剂塞来昔布一线联合化疗能改善疾病控制率,患者耐受性好。血清DKK1水平可能是预测塞来昔布治疗疗效及预后的潜在生物标志物,尚需要大样本的研究证实。Objective To evaluate the anti-tumor effect and safety of cyclooxygenase(COX-2) inhibitor celecoxib in the treatment for advanced non-small cell lung caner(NSCLC), and to investigate the action mechanism of COX-2 inhibitors by detecting serum DKK1 levels. Methods A total of 81 untreated patients with stage Ⅲ-Ⅳ NSCLC were randomized into treatment group(vinorelbine/cisplatin+celecoxib) and control group(vinorelbine/cisplatin). The patients' serum DKK1 levels were detected by ELISA assay at different time points before initial chemotherapy and after chemotherapy. Results The two groups showed significant difference in ORR(34.1% vs 15.0%, P<0.05). Progression-free survival(PFS) in the treatment group was superior to that in the control group, but there was no significance(6.3 m vs 5.9 m). Serum DKK1 levels in the treatment group after chemotherapy were significantly lower than that before chemotherapy(P=0.032). The reduction of serum DKK1 levels after chemotherapy in the treatment group were significantly correlated with patients' PFS(P=0.043). Conclusion COX-2 inhibitor celecoxib can improve ORR of cisplatin-based chemotherapy. The patient's serum DKK1 level is a good biomarker to predict efficacy and prognosis.

关 键 词：环氧合酶-2(COX-2) 塞来昔布 DKK1 化疗 非小细胞肺癌(NSCLC) 

分 类 号：R734.2[医药卫生—肿瘤]