Journal
ONCOTARGETS AND THERAPY
Volume 11, Issue -, Pages 721-730Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/OTT.S148670
Keywords
cyclooxygenase-2 inhibitors; non-small-cell lung cancer; chemotherapy; overall survival; meta-analysis
Categories
Funding
- science and technology activities among overseas students and Molecular Genetics and Mechanism of EGFR Gene Mutation in Uygur and Han People with NSCLC in Xinjiang Applying Circulating Tumor DNA Detection [81560381]
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Background: The study of cyclooxygenase-2 (COX-2) inhibitors is now mired in controversy. We performed a meta-analysis to assess the efficacy and safety profile of COX-2 inhibitors in patients with advanced non-small-cell lung cancer (NSCLC). Patients and methods: A literature search of PubMed, EMBASE, the Cochrane Central databases, and ClinicalTrials.gov, up until March 26, 2017, identified relevant randomized controlled trials. Data analysis was performed using Stata 12.0. Results: Six eligible trials (1,794 patients) were selected from the 407 studies that were identified initially. A significant difference, favoring COX-2 inhibitors plus chemotherapy over chemotherapy alone, was observed in the overall response rate (relative risk [RR] = 1.25, 95% confidence interval [CI]: 1.06-1.48). Further, we conducted two subgroup analyses according to the type of COX-2 inhibitors (celecoxib, rofecoxib, or apricoxib) and treatment line (first or second chemotherapy). The first-line treatment includes: NP (changchun red bean + cisplatin or carboplatin), GP (double fluorine cytidine + cisplatin or carboplatin), or TP (paclitaxel + cisplatin or carboplatin, docetaxel + cisplatin or carboplatin). The second-line treatment includes two internationally recognized compounds, one is docetaxel and the other is the pemetrexed, both of which are individually selected. In subgroup analysis, significantly increased overall response rate (ORR) results were found for rofecoxib plus chemotherapy (RR = 1.56, 95% CI: 1.08-2.25) and COX-2 inhibitor given with first-line chemotherapy (RR = 1.27, 95% CI: 1.07-1.50). However, there was no difference between COX-2 inhibitors plus chemotherapy and chemotherapy alone in overall survival (hazard ratio [HR] = 1.04, 95% CI: 0.91-1.18), progression-free survival (HR = 0.97, 95% CI: 0.86-1.10), and 1-year survival rate (RR = 1.03, 95% CI: 0.89-1.20). Toxicity did not differ significantly between COX-2 inhibitors plus chemotherapy and chemotherapy alone with the exception of leukopenia (RR = 1.21, 95% CI: 1.03-1.42), thrombocytopenia (RR = 1.32, 95% CI: 1.04-1.67), and cardiovascular events (RR = 2.39, 95% CI: 1.06-5.42). The results of the Egger's test indicated no significant difference in primary outcomes. Conclusion: COX-2 inhibitors improved ORR of advanced NSCLC with chemotherapy, but had no effect on survival indices. Moreover, COX-2 inhibitors may lead to higher rates of hematologic toxicities and cardiovascular events.
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