Systematic Reviews
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jan 26, 2021; 9(3): 581-601
Published online Jan 26, 2021. doi: 10.12998/wjcc.v9.i3.581
Clinical benefit of COX-2 inhibitors in the adjuvant chemotherapy of advanced non-small cell lung cancer: A systematic review and meta-analysis
Yu-Qiong Xu, Xiang Long, Ming Han, Ming-Qiang Huang, Jia-Fa Lu, Xue-Dong Sun, Wei Han
Yu-Qiong Xu, Ming Han, Ming-Qiang Huang, Jia-Fa Lu, Xue-Dong Sun, Wei Han, Department of Emergency Medicine, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen 518000, Guangdong Province, China
Xiang Long, Department of Respiratory and Critical Care Medicine, Peking University Shenzhen Hospital, Shenzhen 518000, Guangdong Province, China
Author contributions: Han W and Xu YQ contributed to the study conception and design, the acquisition of data, and the drafting of the manuscript; Xu YQ, Long X, Han M, Huang MQ, Lu JF, and Sun XD contributed to the analysis and interpretation of the quantitative data and the drafting of the manuscript; Xu YQ, Long X, and Han M contributed to the development of critical revising of the final draft; Xu YQ and Han W contributed to the analysis and interpretation of the descriptive and revising the final draft; All authors have read and approved the manuscript.
Supported by The Sanming Project of Medicine in Shenzhen, No. SZSM201911007.
Conflict-of-interest statement: The authors have declared that no conflict-of-interest exist.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Wei Han, MD, Associate Chief Physician, Department of Emergency Medicine, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, No. 1098 Xueyuan Avenue, Shenzhen 518000, Guangdong Province, China. sugh_hanwei@szu.edu.cn
Received: July 15, 2020
Peer-review started: July 15, 2020
First decision: September 29, 2020
Revised: October 17, 2020
Accepted: November 9, 2020
Article in press: November 9, 2020
Published online: January 26, 2021
Abstract
BACKGROUND

Lung cancer is a major cause of death among patients, and non-small cell lung cancer (NSCLC) accounts for more than 80% of all lung cancers in many countries.

AIM

To evaluate the clinical benefit (CB) of COX-2 inhibitors in patients with advanced NSCLC using systematic review.

METHODS

We searched the six electronic databases up until December 9, 2019 for studies that examined the efficacy and safety of the addition of COX-2 inhibitors to chemotherapy for NSCLC. Overall survival (OS), progression free survival (PFS), 1-year survival rate (SR), overall response rate (ORR), CB, complete response (CR), partial response (PR), stable disease (SD), and toxicities were measured with more than one outcome as their endpoints. Fixed and random effects models were used to calculate risk estimates in a meta-analysis. Potential publication bias was calculated using Egger’s linear regression test. Data analysis was performed using R software.

RESULTS

The COX-2 inhibitors combined with chemotherapy were not found to be more effective than chemotherapy alone in OS, progression free survival, 1-year SR, CB, CR, and SD. However, there was a difference in overall response rate for patients with advanced NSCLC. In a subgroup analysis, significantly increased ORR results were found for celecoxib, rofecoxib, first-line treatment, and PR. For adverse events, the increase in COX-2 inhibitor was positively correlated with the increase in grade 3 and 4 toxicity of leukopenia, thrombocytopenia, and cardiovascular events.

CONCLUSION

COX-2 inhibitor combined with chemotherapy increased the total effective rate of advanced NSCLC with the possible increased risk of blood toxicity and cardiovascular events and had no effect on survival index.

Keywords: Non-small cell lung cancer, COX-2, Survival, Progression free survival, Systematic review, Randomized controlled trials

Core Tip: This study demonstrated that in patients who received adjuvant chemotherapy for advanced non-small cell lung cancer, COX-2 inhibitors improved the overall response rate and had no improvement on prolonged mortality. However, COX-2 enhanced both the overall response rate and the 1-year survival rate. Concerning toxicity, celecoxib plus chemotherapy resulted in a higher incidence of hematologic toxicities. Meanwhile, rofecoxib may augment the risk of cardiovascular events.