Aspirin and COX-2 inhibitor use in patients with stage III colon cancer.

We conducted a prospective, observational study of aspirin and COX-2 inhibitor use and survival in stage III colon cancer patients enrolled in an adjuvant chemotherapy trial. Among 799 eligible patients, aspirin use was associated with improved recurrence-free survival (RFS) (multivariable hazard ratio [HR] = 0.51, 95% confidence interval [CI] = 0.28 to 0.95), disease-free survival (DFS) (HR = 0.68, 95% CI = 0.42 to 1.11), and overall survival (OS) (HR = 0.63, 95% CI = 0.35 to 1.12). Adjusted HRs for DFS and OS censored at five years (in an attempt to minimize misclassification from noncancer death) were 0.61 (95% CI = 0.36 to 1.04) and 0.48 (95% CI = 0.23 to 0.99). Among 843 eligible patients, those who used COX-2 inhibitors had multivariable HRs for RFS, DFS, and OS of 0.53 (95% CI = 0.27 to 1.04), 0.60 (95% CI = 0.33 to 1.08), and 0.50 (95% CI = 0.23 to 1.07), and HRs of 0.47 (95% CI = 0.24 to 0.91) and 0.26 (95% CI = 0.08 to 0.81) for DFS and OS censored at five years. Aspirin and COX-2 inhibitor use may be associated with improved outcomes in stage III colon cancer patients.

[1]  P. Kuppen,et al.  Expression of HLA class I antigen, aspirin use, and survival after a diagnosis of colon cancer. , 2014, JAMA internal medicine.

[2]  D. Kerr,et al.  Evaluation of PIK3CA mutation as a predictor of benefit from nonsteroidal anti-inflammatory drug therapy in colorectal cancer. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  Molin Wang,et al.  Aspirin use and risk of colorectal cancer according to BRAF mutation status. , 2013, JAMA.

[4]  A. D. de Craen,et al.  Aspirin Use After Diagnosis Improves Survival in Older Adults with Colon Cancer: A Retrospective Cohort Study , 2012, Journal of the American Geriatrics Society.

[5]  Reiko Nishihara,et al.  Aspirin use, tumor PIK3CA mutation, and colorectal-cancer survival. , 2012, The New England journal of medicine.

[6]  A. Walker,et al.  Aspirin and other non-steroidal anti-inflammatory drug use and colorectal cancer survival: a cohort study , 2012, British Journal of Cancer.

[7]  P. Rothwell,et al.  Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials , 2012, The Lancet.

[8]  Gianni Tognoni,et al.  Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials , 2012, The Lancet.

[9]  O. Dekkers,et al.  Use of Aspirin postdiagnosis improves survival for colon cancer patients , 2012, British Journal of Cancer.

[10]  Rodney J Scott,et al.  Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial , 2011, The Lancet.

[11]  R. Ali,et al.  The utility of Aspirin in dukes C and high risk dukes B colorectal cancer - The ASCOLT study: study protocol for a randomized controlled trial , 2011, Trials.

[12]  P. Rothwell,et al.  Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials , 2011, The Lancet.

[13]  A. Algra,et al.  Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials , 2010, The Lancet.

[14]  C. Ulrich,et al.  Prediagnostic non-steroidal anti-inflammatory drug use and survival after diagnosis of colorectal cancer , 2010, Gut.

[15]  M. Karin,et al.  Immunity, Inflammation, and Cancer , 2010, Cell.

[16]  D. Stram,et al.  Nonsteroidal anti‐inflammatory drugs , 2009, Cancer.

[17]  S. Ogino,et al.  Aspirin Use and Survival After Diagnosis of Colorectal Cancer , 2009 .

[18]  P. Delvenne,et al.  Epithelial metaplasia: adult stem cell reprogramming and (pre)neoplastic transformation mediated by inflammation? , 2009, Trends in molecular medicine.

[19]  A. Riggs,et al.  Methylation of polycomb target genes in intestinal cancer is mediated by inflammation. , 2008, Cancer research.

[20]  Katerina Akassoglou,et al.  NF-κB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1α , 2008, Nature.

[21]  R. Goldberg,et al.  Irinotecan fluorouracil plus leucovorin is not superior to fluorouracil plus leucovorin alone as adjuvant treatment for stage III colon cancer: results of CALGB 89803. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[22]  J. Manson,et al.  Long-term aspirin use and mortality in women. , 2007, Archives of internal medicine.

[23]  J. Baron,et al.  A randomized trial of rofecoxib for the chemoprevention of colorectal adenomas. , 2006, Gastroenterology.

[24]  S. Solomon,et al.  Celecoxib for the prevention of sporadic colorectal adenomas. , 2006, The New England journal of medicine.

[25]  K. Druey,et al.  Prostaglandin E2 Promotes Colon Cancer Cell Growth Through a Gs-Axin-ß-Catenin Signaling Axis , 2005, Science.

[26]  J. Manson,et al.  Low-Dose Aspirin in the Primary Prevention of Cancer: The Women’s Health Study: A Randomized Controlled Trial , 2005, JAMA.

[27]  J. Meyerhardt,et al.  Influence of regular aspirin use on survival for patients with stage III colon cancer: Findings from Intergroup trial CALGB 89803 , 2005 .

[28]  S. Anant,et al.  Prostaglandin E2 reduces radiation-induced epithelial apoptosis through a mechanism involving AKT activation and bax translocation. , 2004, The Journal of clinical investigation.

[29]  J. Morrow,et al.  Colon Carcinoma Cell Growth Is Associated with Prostaglandin E2/EP4 Receptor-evoked ERK Activation* , 2004, Journal of Biological Chemistry.

[30]  Yoichi Tanaka,et al.  Recurrence patterns after curative resection of colorectal cancer in patients followed for a minimum of ten years. , 2003, Hepato-gastroenterology.

[31]  G. Beck,et al.  A Randomized Trial of Aspirin to Prevent Colorectal Adenomas , 2003 .

[32]  J. Little,et al.  Daily soluble aspirin and prevention of colorectal adenoma recurrence: one-year results of the APACC trial. , 2003, Gastroenterology.

[33]  J. Potter,et al.  Reliability and validity of self-report of vitamin and mineral supplement use in the vitamins and lifestyle study. , 2003, American journal of epidemiology.

[34]  Susan Halabi,et al.  A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer. , 2003, The New England journal of medicine.

[35]  B. Levin,et al.  The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. , 2000, The New England journal of medicine.

[36]  J. Crowley,et al.  A general class of nonparametric tests for survival analysis. , 1989, Biometrics.

[37]  E. Kaplan,et al.  Nonparametric Estimation from Incomplete Observations , 1958 .

[38]  Edward L. Melnick,et al.  Modeling Survival Data , 2011, International Encyclopedia of Statistical Science.

[39]  P. Loehrer.  Celecoxib for the Prevention of Colorectal Adenomatous Polyps , 2008 .

[40]  K. Muir,et al.  Aspirin and folic acid for the prevention of recurrent colorectal adenomas. , 2008, Gastroenterology.