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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 2 (COX-2) inhibitors by treating patients with advanced non-small cell lung cancer (NSCLC) through celecoxib combined with platinum chemotherapy. Serum DKK1 monitoring the COX-2 inhibitor-related mechanism of action and predictors of efficacy. Methods Totally 81 patients with stage Ⅲ-Ⅳ NSCLC were randomly divided into treatment group (vinorelbine / cisplatin + celecoxib group) and control group (vinorelbine / cisplatin group). Until the fourth course of treatment and follow-up progress. Serum DKK1 levels were measured by ELISA before treatment and after 2 courses of chemotherapy. Results The objective response rate (ORR) was 34.1% in the treatment group and 15.0% in the control group, with significant difference between the two groups (P <0.05). The progression-free survival (PFS) was slightly longer in the treatment group (6.3 months) The group was 5.9 months, but the difference did not reach statistical significance. There was no difference in serum DKK1 level between the two groups before treatment, and there was no statistically significant correlation between age, gender, pathological type, stage, smoking status and ECOG score. After 2 courses of chemotherapy, serum DKK1 level of both groups showed a downward trend, but the decline of serum DKK1 in the treatment group was significantly greater than that of the control group (median reduction was 37.58 vs 2.83 pg / ml, P = 0.01); After treatment Serum DKK1 levels were significantly lower than before treatment (P <0.05), the control group before and after treatment was not significantly different. Serum DKK1 levels before and after treatment in both groups were not significantly correlated with the efficacy of chemotherapy (P = 0.908, 0.730, 0.515, 0.413, respectively). Serum DKK1 levels before treatment in both groups were not significantly correlated with PFS (P = 0.090,0.890). However, the decline in serum DKK1 level after chemotherapy in patients with celecoxib was significantly associated with PFS (P = 0.043). Conclusion COX-2 inhibitor celecoxib combined with chemotherapy can improve the disease control rate, and patients are well tolerated. Serum DKK1 level may be a potential biomarker for predicting the efficacy and prognosis of celecoxib, but large sample studies are needed.