Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2016 Mar 23;11(3):e0151939.
doi: 10.1371/journal.pone.0151939. eCollection 2016.

Clinical Profile of Cyclooxygenase-2 Inhibitors in Treating Non-Small Cell Lung Cancer: A Meta-Analysis of Nine Randomized Clinical Trials

Yuan Yuan Zhou  1 , Zhi Gang Hu  1 , Fan Jun Zeng  1 , Jiao Han  1
Affiliations
Meta-Analysis

Clinical Profile of Cyclooxygenase-2 Inhibitors in Treating Non-Small Cell Lung Cancer: A Meta-Analysis of Nine Randomized Clinical Trials

Yuan Yuan Zhou et al. PLoS One. .

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Flow chart indicates the selection of studies.
RCT = randomized clinical trial.
Fig 2
Fig 2. Consensus risk of bias assessments of the included studies.
Green: Low risk, Yellow: Unclear, Red: High risk.
Fig 3
Fig 3. Forest plot of the (A) ORR and (B) one-year survival in patients with NSCLC randomly assigned to COX-2 inhibitors treatment versus placebo/no intervention.
ORR = overall response rate.
Fig 4
Fig 4. Funnel plot of risk ratio for studies included in the meta-analysis.
analysis. (A)ORR, P = 0.43, Egger’s test; (B) one-year survival, P = 0.297, Egger’s test. ORR = overall response rate.
See this image and copyright information in PMC

References

    1. Gronberg BH, Bremnes RM, Flotten O, Amundsen T, Brunsvig PF, Hjelde HH,et al. (2009) Phase III study by the Norwegian lung cancer study group: pemetrexed plus carboplatin compared with gemcitabine plus carboplatin as first-line chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol 27:3217–24. 10.1200/JCO.2008.20.9114 - DOI - PubMed
    1. Helbekkmo N, Sundstrom SH, Aasebo U, Brunsvig PF, von Plessen C, Hjelde HH, et al. (2007) Vinorelbine/carboplatin vs. gemcitabine/carboplatin in advanced NSCLC shows similar efficacy, but different impact of toxicity. Br J Cancer 97:283–9. - PMC - PubMed
    1. Sederholm C, Hillerdal G, Lamberg K, Kölbeck K, Dufmats M, Westberg R,et al. (2005) Phase III trial of gemcitabine plus carboplatin versus single-agent gemcitabine in the treatment of locally advanced or metastatic non-small-cell lung cancer: the Swedish Lung Cancer Study Group. J Clin Oncol 23:8380–8 - PubMed
    1. Von Plessen C, Bergman B, Andresen O, Bremnes RM, Sundstrom S, Gilleryd M,et al. (2006) Palliative chemotherapy beyond three courses conveys no survival or consistent quality-of-life benefits in advanced non-small-cell lung cancer. Br J Cancer 95:966–73. - PMC - PubMed
    1. Qi WX, Fu S, Zhang Q,Guo XM.(2015) Anti-epidermal-growth-factor-receptor Agents and complete responses in the treatment of advanced non-small-cell lung cancer: a meta-analysis of 17 phase III randomized controlled trials. Curr Med Res Opin 31:25–33. 10.1185/03007995.2014.978448 - DOI - PubMed

Publication types

MeSH terms

Substances