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World Journal of Surgical Oncology

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Open Access 01-12-2015 | Research

Cyclooxygenase-2 expression is a prognostic biomarker for non-small cell lung cancer patients treated with adjuvant platinum-based chemotherapy

Authors: Katsuhiko Shimizu, Takuro Yukawa, Riki Okita, Shinsuke Saisho, Ai Maeda, Yuji Nojima, Masao Nakata

Published in: World Journal of Surgical Oncology | Issue 1/2015

Abstract

Background

Adjuvant chemotherapy after the resection of stage IB-IIIA non-small cell lung cancer (NSCLC) is now the standard of care based on large-scale phase III trials and a meta-analysis. However, chemotherapy has plateaued in terms of its efficacy, and the search for treatment prediction biomarkers is imperative for the further identification of treatable subgroups. Therefore, we investigated the significance of cyclooxygenase-2 (Cox-2) expression and the applicability of a Cox-2 inhibitor in patients who had received adjuvant chemotherapy.

Methods

We conducted a retrospective review of data from 97 patients who had received adjuvant chemotherapy. The adjuvant chemotherapy consisted of an oral tegafur agent (OT) or platinum-based chemotherapy (PB). The criteria for regimen selection were based on a discussion among the cancer board and enrollment in a clinical trial. Immunohistochemical staining (IHC) for Cox-2 was performed, and the correlation between Cox-2 expression and disease-free survival (DFS) was evaluated.

Results

IHC showed that 56 cases (57.7%) were positive for Cox-2. The rate of Cox-2 expression was similar for the PB and OT groups. Among the patients who received PB, the DFS of the patients with Cox-2 expression was significantly poorer than that of the patients without Cox-2 expression (P = 0.017), but there was no significant difference among the patients who received OT (P = 0.617). In a multivariate analysis, Cox-2 expression and lymph node metastasis were independent predictors of DFS among patients who received PB.

Conclusions

Cox-2 expression was a powerful predictor of DFS among patients who received PB as an adjuvant chemotherapy. Further study investigating the use of a Cox-2 inhibitor for adjuvant chemotherapy is needed.

Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004;350:351–60.CrossRefPubMed

Winton T, Livingston R, Johnson D, Rigas J, Johnston M, Butts C, et al. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med. 2005;352:2589–97.CrossRefPubMed

Douillard JY, Rosell R, De Lena M, Carpagnano F, Ramlau R, Gonzáles-Larriba JL, et al. Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial. Lancet Oncol. 2006;7:719–27.CrossRefPubMed

Pignon JP, Tribodet H, Scagliotti GV, Douillard JY, Shepherd FA, Stephens RJ, et al. Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE collaborative group. J Clin Oncol. 2008;26:3552–9.CrossRefPubMed

Asamura H, Goya T, Koshiishi Y, Sohara Y, Eguchi K, Mori M, et al. A Japanese lung cancer registry study: prognosis of 13,010 resected lung cancers. J Thorac Oncol. 2008;3:46–52.CrossRefPubMed

Asamura H, Nakayama H, Kondo H, Tsuchiya R, Naruke T. Lobe-specific extent of systematic lymph node dissection for non-small cell lung carcinomas according to a retrospective study of metastasis and prognosis. J Thorac Cardiovasc Surg. 1999;117:1102–11.CrossRefPubMed

Mitsudomi T, Suda K, Yatabe Y. Surgery for NSCLC in the era of personalized medicine. Nat Rev. 2013;10:235–44.

Dubois RN, Abramson SB, Crofford L, Gupta RA, Simon LS, Van De Putte LB, et al. Cyclooxygenase in biology and disease. FASEB J. 1998;12:1063–73.PubMed

Hida T, Yatabe Y, Achiwa H, Muramatsu H, Kozaki K, Nakamura S, et al. Increased expression of cyclooxygenase 2 occurs frequently in human lung cancers, specifically in adenocarcinomas. Cancer Res. 1998;58:3761–4.PubMed

10.

Hwang D, Scollard D, Byrne J, Levine E. Expression of cyclooxygenase-1 and cyclooxygenase-2 in human breast cancer. J Natl Cancer Inst. 1998;90:455–60.CrossRefPubMed

11.

Ogino S, Kirkner GJ, Nosho K, Irahara N, Kure S, Shima K, et al. Cyclooxygenase-2 expression is an independent predictor of poor prognosis in colon cancer. Clin Cancer Res. 2008;14:8221–7.CrossRefPubMedCentralPubMed

12.

Edelman MJ, Watson D, Wang X, Morrison C, Kratzke RA, Jewell S, 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;26:848–55.CrossRefPubMed

13.

Hamada C, Tsuboi M, Ohta M, Fujimura S, Kodama K, Imaizumi M, et al. Effect of postoperative adjuvant chemotherapy with tegafur-uracil on survival in patients with stage IA non-small cell lung cancer: an exploratory analysis from a meta-analysis of six randomized controlled trials. J Thorac Oncol. 2009;4:1511–6.CrossRefPubMed

14.

Lord RV, Brabender J, Gandara D, Alberola V, Camps C, Domine M, et al. Low ERCC1 expression correlates with prolonged survival after cisplatin plus gemcitabine chemotherapy in non-small cell lung cancer. Clin Cancer Res. 2002;8:2286–91.PubMed

15.

Olaussen KA, Dunant A, Fouret P, Brambilla E, André F, Haddad V, et al. DNA repair by ERCC1 in non-small cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med. 2006;355:983–91.CrossRefPubMed

16.

Seve P, Mackey J, Isaac S, Tredan O, Souquet PJ, Perol M, et al. Class III β-tubulin expression in tumor cells predicts response and outcome in patients with non-small cell lung cancer receiving paclitaxel. Mol Cancer Ther. 2005;4:2001–7.CrossRefPubMed

17.

Reiman T, Lai R, Veillard AS, Paris E, Soria JC, Rosell R, et al. Cross-validation study of class III beta-tubulin as a predictive marker for benefit from adjuvant chemotherapy in resected non-small-cell lung cancer: analysis of four randomized trials. Ann Oncol. 2012;23:86–93.CrossRefPubMedCentralPubMed

18.

Bepler G, Williams C, Schell MJ, Chen W, Zheng Z, Simon G, et al. Randomized international phase III trial of ERCC1 and RRM1 expression-based chemotherapy versus gemcitabine/carboplatin in advanced non-small-cell lung cancer. J Clin Oncol. 2013;31:2404–12.CrossRefPubMedCentralPubMed

19.

Kato H, Ichinose Y, Ohta M, Hata E, Tsubota N, Tada H, et al. A randomized trial of adjuvant chemotherapy with uracil-tegafur for adenocarcinoma of the lung. N Engl J Med. 2004;350:1713–21.CrossRefPubMed

20.

Okamoto I, Yoshioka H, Morita S, Ando M, Takeda K, Seto T, et al. Phase III trial comparing oral S-1 plus carboplatin with paclitaxel plus carboplatin in chemotherapy-naïve patients with advanced non-small-cell lung cancer: results of a west Japan oncology group study. J Clin Oncol. 2010;28:5240–6.CrossRefPubMed

21.

Nakano J, Huang C, Liu D, Masuya D, Nakashima T, Yokomise H, et al. Evaluations of biomarkers associated with 5-FU sensitivity for non-small cell lung cancer patients postoperatively treated with UFT. Br J Cancer. 2006;95:607–15.CrossRefPubMedCentralPubMed

22.

Masferrer JL, Leahy KM, Koki AT, Zweifel BS, Settle SL, Woerner BM, et al. Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors. Cancer Res. 2000;60:1306–11.PubMed

23.

Brabender J, Park J, Metzger R, Schneider PM, Lord RV, Hölscher AH, et al. Prognostic significance of cyclooxygenase 2 mRNA expression in non-small cell lung cancer. Ann Surg. 2002;235:440–3.CrossRefPubMedCentralPubMed

24.

Khuri FR, Wu H, Lee JJ, Kemp BL, Lotan R, Lippman SM, et al. Cyclooxygenase-2 overexpression is a marker of poor prognosis in stage I non-small cell lung cancer. Clin Cancer Res. 2001;7:861–7.PubMed

25.

Altorki NK, Keresztes RS, Port JL, Libby DM, Korst RJ, Flieder DB, et al. Celecoxib, a selective cyclo-oxygenase-2 inhibitor, enhances the response to preoperative paclitaxel and carboplatin in early-stage non-small-cell lung cancer. J Clin Oncol. 2003;21:2645–50.CrossRefPubMed

26.

Mascaux C, Martin B, Paesmans M, Berghmans T, Dusart M, Haller A, et al. Has Cox-2 a prognostic role in non-small-cell lung cancer? A systematic review of the literature with meta-analysis of the survival results. Br J Cancer. 2006;95:139–45.CrossRefPubMedCentralPubMed

27.

Groen HJ, Sietsma H, Vincent A, Hochstenbag MM, van Putten JW, van den Berg A, et al. Randomized, placebo-controlled phase III study 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;29:4320–6.CrossRefPubMed

28.

Tanaka F, Takenaka K, Yanagihara K, Fukushima M, Wada H. COX-2 status is significant factor to predict a postoperative survival as well as an efficacy of postoperative adjuvant therapy in non-small cell lung cancer. J Clin Oncol. 2004;22:9556.

29.

Duarte ML, de Moraes E, Pontes E, Schluckebier L, de Moraes JL, Hainaut P, et al. Role of p53 in the induction of cyclooxygenase-2 by cisplatin or paclitaxel in non-small cell lung cancer cell lines. Cancer Lett. 2009;28:57–64.CrossRef

Title: Cyclooxygenase-2 expression is a prognostic biomarker for non-small cell lung cancer patients treated with adjuvant platinum-based chemotherapy
Authors: Katsuhiko Shimizu
Takuro Yukawa
Riki Okita
Shinsuke Saisho
Ai Maeda
Yuji Nojima
Masao Nakata
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: World Journal of Surgical Oncology / Issue 1/2015
Electronic ISSN: 1477-7819
DOI: https://doi.org/10.1186/s12957-014-0426-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Cyclooxygenase-2 expression is a prognostic biomarker for non-small cell lung cancer patients treated with adjuvant platinum-based chemotherapy

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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