Zhou Yuan Yuan, Hu Zhi Gang, Zeng Fan Jun, Han Jiao
Department of Respiratory medicine, The first College of Clinical Medicine science, Three Gorges University, Yichang, 443003, People's Republic of China.
PLoS One. 2016 Mar 23;11(3):e0151939. doi: 10.1371/journal.pone.0151939. eCollection 2016.
Evidence on the benefits of combining cyclooxygenase-2 inhibitor (COX-2) in treating non-small cell lung cancer (NSCLC) is still controversial. We investigated the efficacy and safety profile of cyclooxygenase-2 inhibitors in treating NSCLC.
The first meta-analysis of eligible studies was performed to assess the effect of COX-2 inhibitors for patients with NSCLC on the overall response rate (ORR), overall survival (OS), progression-free survival (PFS), one-year survival, and toxicities. The fixed-effects model was used to calculate the pooled RR and HR and between-study heterogeneity was assessed. Subgroup analyses were conducted according to the type of COX-2 inhibitors, treatment pattern, and treatment line.
Nine randomized clinical trials, comprising 1679 patents with NSCLC, were included in the final meta-analysis. The pooled ORR of patients who have NSCLC with COX-2 inhibitors was significantly higher than that without COX-2 inhibitors. In subgroup analysis, significantly increased ORR results were found on celecoxib (RR = 1.29, 95% CI: 1.09, 1.51), rofecoxib (RR = 1.61, 95% CI: 1.14, 2.28), chemotherapy (RR = 1.40, 95% CI: 1.20, 1.63), and first-line treatment (RR = 1.39, 95% CI: 1.19, 1.63). However, COX-2 inhibitors had no effect on the one-year survival, OS, and PFS. Increased RR of leucopenia (RR = 1.21, 95% CI: 1.01, 1.45) and thrombocytopenia (RR = 1.36, 95% CI: 1.06, 1.76) suggested that COX-2 inhibitors increased hematologic toxicities (grade ≥ 3) of chemotherapy.
COX-2 inhibitors increased ORR of advanced NSCLC and had no impact on survival indices, but it may increase the risk of hematologic toxicities associated with chemotherapy.
关于联合使用环氧化酶-2抑制剂(COX-2)治疗非小细胞肺癌(NSCLC)的益处的证据仍存在争议。我们研究了环氧化酶-2抑制剂治疗NSCLC的疗效和安全性。
对符合条件的研究进行首次荟萃分析,以评估COX-2抑制剂对NSCLC患者的总缓解率(ORR)、总生存期(OS)、无进展生存期(PFS)、一年生存率和毒性的影响。采用固定效应模型计算合并RR和HR,并评估研究间的异质性。根据COX-2抑制剂的类型、治疗模式和治疗线进行亚组分析。
最终的荟萃分析纳入了9项随机临床试验,共1679例NSCLC患者。使用COX-2抑制剂的NSCLC患者的合并ORR显著高于未使用COX-2抑制剂的患者。在亚组分析中,塞来昔布(RR = 1.29,95%CI:1.09,1.51)、罗非昔布(RR = 1.61,95%CI:1.14,2.28)、化疗(RR = 1.40,95%CI:1.20,1.63)和一线治疗(RR = 1.39,95%CI:1.19,1.63)的ORR结果显著增加。然而,COX-2抑制剂对一年生存率、OS和PFS没有影响。白细胞减少症(RR = 1.21,95%CI:1.01,1.45)和血小板减少症(RR = 1.36,95%CI:1.06,1.76)的RR增加表明COX-2抑制剂增加了化疗的血液学毒性(≥3级)。
COX-2抑制剂增加了晚期NSCLC的ORR,对生存指标没有影响,但可能增加与化疗相关的血液学毒性风险。