Efficacy and Safety of Cyclooxygenase-2 Signal Pathway Inhibition in Treating Advanced Non-small Cell Lung Cancer: A Systematic Review and Meta-analysis_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

DENGHan-yu ^1,2 , WANGYun-cang ¹ , WANGXi ² , FANShu-cai ² ,  LINYi-dan ¹

1. Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;
2. West China School of Medicine, Sichuan University, Chengdu 610041, P. R. China;

Corresponding author：

LINYi-dan, Email: linyidan@scu.edu.cn

Keywords：

Cyclooxygenase-2 (COX-2) inhibitors; Non-small cell lung cancer (NSCLC); Systematic review/Meta-analysis

DOI：

10.7507/1007-4848.20160036

Video：

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Objective To systemically evaluate the efficacy and safety of cyclooxygenase-2 (COX-2) signal pathway inhibition in treating advanced non-small cell lung cancer (NSCLC). Methods A systematic literature search in PubMed, EMbase, Cochrane Library, ASCO databases, CNKI and Wanfang database was conducted to identify relevant randomized controlled trials (RCTs) from the time of database establishment to June 2015. RCTs of COX-2 inhibitors treating advanced NSCLC were included. We assessed the methodology quality of the included studies by using Jadad's scale, and performed this meta-analysis by using stata12.0 software. Results Twelve RCTs involving three different COX-2 inhibitors with a total of 1 828 patients were identified including 8 studies of high quality and 4 studies of low quality. We found that COX-2 signal pathway inhibition could significantly increase overall response rate at RR=1.27 with 95%CI1.10 to 1.46 (P=0.001). While our present data could not confirm the efficacy of COX-2 inhibitors in improving progression-free survival (PFS) at HR=0.93 with 95%CI0.81 to 1.08 (P=0.334), overall survival (OS) at HR=0.95 with 95%CI0.84 to 1.08 (P=0.461), or one-year survival rate at RR=1.08 with 95%CI0.90 to 1.24 (P=0.29). As for toxicities, only increased risk of thrombocytopenia at RR=1.28 with 95%CI 1.03 to 1.85 (P=0.03) was observed in the patients treated with COX-2 inhibitors. Conclusion COX-2 signal pathway inhibition is effective in improving the overall response rate of the patients with advanced NSCLC, and is well tolerated. Whether COX-2 signal pathway inhibition is effective in improving long-term survival of the patients with advanced NSCLC still needs to be confirmed via further clinical trials.

Citation： DENGHan-yu, WANGYun-cang, WANGXi, FANShu-cai, LINYi-dan. Efficacy and Safety of Cyclooxygenase-2 Signal Pathway Inhibition in Treating Advanced Non-small Cell Lung Cancer: A Systematic Review and Meta-analysis. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2016, 23(2): 160-167. doi: 10.7507/1007-4848.20160036 Copy

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5.	Reckamp K, Gitlitz B, Chen LC, et al. Biomarker-based phase I dose-escalation, pharmacokinetic, and pharmacodynamic study of oral apricoxib in combination with erlotinib in advanced nonsmall cell lung cancer. Cancer, 2011, 117(4): 809-818.
6.	Chen J, Shen P, Zhang XC, et al. Efficacy and safety profile of cele-coxib for treating advanced cancers: a meta-analysis of 11 randomized clinical trials. Clin Ther, 2014, 36(8): 1253-1263.
7.	任春利, 缪李丽.塞来昔布联合放化疗对比单纯放化疗治疗晚期非小细胞肺癌疗效与安全性的Meta分析.中国药房, 2014, 44: 4198-4202.
8.	Liu CH, Bao HG, Ge YL, et al. Celecoxib inhibits insulin-like growth factor 1 induced growth and invasion in non-small cell lung cancer. Oncol Lett, 2013, 5(6): 1943-1947.
9.	Liu B, Qu L, Yang Z, et al. Cyclooxygenase-2 inhibitors induce anoikis in osteosarcoma via PI3K/Akt pathway. Med Hypotheses, 2012, 79(1): 98-100.
10.	Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: Is blinding necessary? Controlled Clinical Trials, 1996, 17(1): 1-12.
11.	Lilenbaum R, Socinski MA, Altorki NK, et al. Randomized phaseⅡtrial of docetaxel/irinotecan and gemcitabine/irinotecan with or without celecoxib in the second-line treatment of non-small-cell lung cancer. J Clin Oncol, 2006, 24(30): 4825-4832.
12.	Gridelli C, Gallo C, Ceribelli A, et al. Factorial phaseⅢrandomised trial of rofecoxib and prolonged constant infusion of gemcitabine in advanced non-small-cell lung cancer: the GEmcitabine-COxib in NSCLC (GECO) study. Lancet Oncol, 2007, 8(6): 500-512.
13.	Groen HJ, Sietsma H, Vincent A, et al. Randomized, placebo-contro-lled phaseⅢstudy of docetaxel plus carboplatin with celecoxib and cyclooxygenase-2 expression as a biomarker for patients with advanced non-small-cell lung cancer: the NVALT-4 study. J Clin Oncol, 2011, 29(32): 4320-4326.
14.	Koch A, Bergman B, Holmberg E, et al. Effect of celecoxib on survival in patients with advanced non-small cell lung cancer: a double blind randomised clinical phaseⅢtrial (CYCLUS study) by the Swedish Lung Cancer Study Group. Eur J Cancer, 2011, 47(10): 1546-1555.
15.	Edelman MJ, Tan MT, Fidler MJ, et al. Randomized, double-blind, placebo-controlled, multicenter phaseⅡstudy of the efficacy and safety of apricoxib in combination with either docetaxel or pemetrexed in patients with biomarker-selected non-small-cell lung cancer. J Clin Oncol, 2015, 33(2): 189-194.
16.	Reckamp KL, Koczywas M, Cristea MC, et al. Randomized phase 2 trial of erlotinib in combination with high-dose celecoxib or placebo in patients with advanced non-small cell lung cancer. Cancer, 2015, 121(18): 3298-3306.
17.	周崧雯, 周彩存, 徐建芳, 等.长春瑞滨和顺铂联合西乐葆一线治疗晚期非小细胞肺癌.同济大学学报(医学版), 2007(05): 87-90, 94.
18.	熊建萍, 项晓军, 张凌, 等.长春瑞滨加顺铂联合COX-2抑制剂治疗晚期非小细胞肺癌临床分析.肿瘤防治研究, 2008(03): 201-203.
19.	何慧娟, 胡伟.塞来昔布联合放化疗治疗晚期肺癌近期疗效观察.中国药师, 2011, 14(4): 531-532.
20.	刘国华, 黄建安.非小细胞肺癌塞来昔布联合化疗的临床观察.中华肿瘤防治杂志, 2012, 21: 1661-1663.
21.	滕家俊, 裴俊, 韩宝惠, 等.血清DKK1水平在塞来昔布一线联合铂类化疗治疗晚期非小细胞肺癌随机对照研究中的临床意义.世界临床药物, 2015, 6: 388-393.
22.	Yokouchi H, Kanazawa K, Ishida T, et al. Cyclooxygenase-2 inhibitors for non-small-cell lung cancer: A phaseⅡtrial and literature review. Mol Clin Oncol, 2014, 2(5): 744-750.
23.	Patel S, Chiplunkar S. Role of cyclooxygenase-2 in tumor progression and immune regulation in lung cancer. Indian J Biochem Biophys, 2007, 44(6): 419-428.
24.	Jiang H, Wang J, Zhao W. Cox-2 in non-small cell lung cancer: a meta-analysis. Clin Chim Acta, 2013, 419: 26-32.
25.	Klenke FM, Abdollahi A, Bischof M, et al. Celecoxib enhances radiation response of secondary bone tumors of a human non-small cell lung cancer via antiangiogenesis in vivo. Strahlenther Onkol, 2011, 187(1): 45-51.
26.	Zhang S, Da L, Yang X, et al. Celecoxib potentially inhibits metastasis of lung cancer promoted by surgery in mice, via suppression of the PGE2-modulated beta-catenin pathway. Toxicol Lett, 2014, 225(2): 201-207.
27.	Edelman MJ, Watson D, Wang X, et al. Eicosanoid modulation in advanced lung cancer: cyclooxygenase-2 expression is a positive predictive factor for celecoxib+chemotherapy--Cancer and Leukemia Group B Trial 30203. J Clin Oncol, 2008, 26(6): 848-855.
28.	Rudd RM, Gower NH, Spiro SG, et al. Gemcitabine plus carboplatin versus mitomycin, ifosfamide, and cisplatin in patients with stageⅢB or IV non-small-cell lung cancer: a phaseⅢrandomized study of the London Lung Cancer Group. J Clin Oncol, 2005, 23(1): 142-153.

1. Wang D, Dubois RN. Prostaglandins and cancer. Gut, 2006, 55(1): 115-122.
2. Abou-Issa H, Alshafie G. Celecoxib: A novel treatment for lung cancer. Expert Rev Anticancer Ther, 2004, 4(5): 725-734.
3. Gitlitz BJ, Bernstein E, Santos ES, et al. A randomized, placebo-controlled, multicenter, biomarker-selected, phase 2 study of apricoxib in combination with erlotinib in patients with advanced non-small-cell lung cancer. J Thorac Oncol, 2014, 9(4): 577-582.
4. Csiki I, Johnson DH. Did targeted therapy fail cyclooxygenase too? J Clin Oncol, 2006, 24(30): 4798-4800.
5. Reckamp K, Gitlitz B, Chen LC, et al. Biomarker-based phase I dose-escalation, pharmacokinetic, and pharmacodynamic study of oral apricoxib in combination with erlotinib in advanced nonsmall cell lung cancer. Cancer, 2011, 117(4): 809-818.
6. Chen J, Shen P, Zhang XC, et al. Efficacy and safety profile of cele-coxib for treating advanced cancers: a meta-analysis of 11 randomized clinical trials. Clin Ther, 2014, 36(8): 1253-1263.
7. 任春利, 缪李丽.塞来昔布联合放化疗对比单纯放化疗治疗晚期非小细胞肺癌疗效与安全性的Meta分析.中国药房, 2014, 44: 4198-4202.
8. Liu CH, Bao HG, Ge YL, et al. Celecoxib inhibits insulin-like growth factor 1 induced growth and invasion in non-small cell lung cancer. Oncol Lett, 2013, 5(6): 1943-1947.
9. Liu B, Qu L, Yang Z, et al. Cyclooxygenase-2 inhibitors induce anoikis in osteosarcoma via PI3K/Akt pathway. Med Hypotheses, 2012, 79(1): 98-100.
10. Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: Is blinding necessary? Controlled Clinical Trials, 1996, 17(1): 1-12.
11. Lilenbaum R, Socinski MA, Altorki NK, et al. Randomized phaseⅡtrial of docetaxel/irinotecan and gemcitabine/irinotecan with or without celecoxib in the second-line treatment of non-small-cell lung cancer. J Clin Oncol, 2006, 24(30): 4825-4832.
12. Gridelli C, Gallo C, Ceribelli A, et al. Factorial phaseⅢrandomised trial of rofecoxib and prolonged constant infusion of gemcitabine in advanced non-small-cell lung cancer: the GEmcitabine-COxib in NSCLC (GECO) study. Lancet Oncol, 2007, 8(6): 500-512.
13. Groen HJ, Sietsma H, Vincent A, et al. Randomized, placebo-contro-lled phaseⅢstudy of docetaxel plus carboplatin with celecoxib and cyclooxygenase-2 expression as a biomarker for patients with advanced non-small-cell lung cancer: the NVALT-4 study. J Clin Oncol, 2011, 29(32): 4320-4326.
14. Koch A, Bergman B, Holmberg E, et al. Effect of celecoxib on survival in patients with advanced non-small cell lung cancer: a double blind randomised clinical phaseⅢtrial (CYCLUS study) by the Swedish Lung Cancer Study Group. Eur J Cancer, 2011, 47(10): 1546-1555.
15. Edelman MJ, Tan MT, Fidler MJ, et al. Randomized, double-blind, placebo-controlled, multicenter phaseⅡstudy of the efficacy and safety of apricoxib in combination with either docetaxel or pemetrexed in patients with biomarker-selected non-small-cell lung cancer. J Clin Oncol, 2015, 33(2): 189-194.
16. Reckamp KL, Koczywas M, Cristea MC, et al. Randomized phase 2 trial of erlotinib in combination with high-dose celecoxib or placebo in patients with advanced non-small cell lung cancer. Cancer, 2015, 121(18): 3298-3306.
17. 周崧雯, 周彩存, 徐建芳, 等.长春瑞滨和顺铂联合西乐葆一线治疗晚期非小细胞肺癌.同济大学学报(医学版), 2007(05): 87-90, 94.
18. 熊建萍, 项晓军, 张凌, 等.长春瑞滨加顺铂联合COX-2抑制剂治疗晚期非小细胞肺癌临床分析.肿瘤防治研究, 2008(03): 201-203.
19. 何慧娟, 胡伟.塞来昔布联合放化疗治疗晚期肺癌近期疗效观察.中国药师, 2011, 14(4): 531-532.
20. 刘国华, 黄建安.非小细胞肺癌塞来昔布联合化疗的临床观察.中华肿瘤防治杂志, 2012, 21: 1661-1663.
21. 滕家俊, 裴俊, 韩宝惠, 等.血清DKK1水平在塞来昔布一线联合铂类化疗治疗晚期非小细胞肺癌随机对照研究中的临床意义.世界临床药物, 2015, 6: 388-393.
22. Yokouchi H, Kanazawa K, Ishida T, et al. Cyclooxygenase-2 inhibitors for non-small-cell lung cancer: A phaseⅡtrial and literature review. Mol Clin Oncol, 2014, 2(5): 744-750.
23. Patel S, Chiplunkar S. Role of cyclooxygenase-2 in tumor progression and immune regulation in lung cancer. Indian J Biochem Biophys, 2007, 44(6): 419-428.
24. Jiang H, Wang J, Zhao W. Cox-2 in non-small cell lung cancer: a meta-analysis. Clin Chim Acta, 2013, 419: 26-32.
25. Klenke FM, Abdollahi A, Bischof M, et al. Celecoxib enhances radiation response of secondary bone tumors of a human non-small cell lung cancer via antiangiogenesis in vivo. Strahlenther Onkol, 2011, 187(1): 45-51.
26. Zhang S, Da L, Yang X, et al. Celecoxib potentially inhibits metastasis of lung cancer promoted by surgery in mice, via suppression of the PGE2-modulated beta-catenin pathway. Toxicol Lett, 2014, 225(2): 201-207.
27. Edelman MJ, Watson D, Wang X, et al. Eicosanoid modulation in advanced lung cancer: cyclooxygenase-2 expression is a positive predictive factor for celecoxib+chemotherapy--Cancer and Leukemia Group B Trial 30203. J Clin Oncol, 2008, 26(6): 848-855.
28. Rudd RM, Gower NH, Spiro SG, et al. Gemcitabine plus carboplatin versus mitomycin, ifosfamide, and cisplatin in patients with stageⅢB or IV non-small-cell lung cancer: a phaseⅢrandomized study of the London Lung Cancer Group. J Clin Oncol, 2005, 23(1): 142-153.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Efficacy and Safety of Cyclooxygenase-2 Signal Pathway Inhibition in Treating Advanced Non-small Cell Lung Cancer: A Systematic Review and Meta-analysis

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