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Cancer Epidemiol Biomarkers Prev. 2018 Jul;27(7):728-736. doi: 10.1158/1055-9965.EPI-17-0573. Epub 2018 May 16.

Chemopreventive Efficacy of the Cyclooxygenase-2 (Cox-2) Inhibitor, Celecoxib, Is Predicted by Adenoma Expression of Cox-2 and 15-PGDH.

Author information

1
Department of Surgery, Division of Surgical Oncology, Brigham and Women's Hospital, Boston, Massachusetts.
2
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
3
Department of Pathology, and Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio.
4
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
5
Department of Pathology, Yale University, New Haven, Connecticut.
6
Departments of Medicine and Case Comprehensive Cancer Center, Case Western Reserve University, and University Hospitals Seidman Cancer Center, Cleveland, Ohio.
7
Department of Surgery, Division of Surgical Oncology, Brigham and Women's Hospital, Boston, Massachusetts. mbertagnolli@partners.org.
#
Contributed equally

Abstract

Background: The Adenoma Prevention with Celecoxib (APC) Trial showed that cyclooxygenase-2 (Cox-2) inhibitor, celecoxib, decreased adenoma development in patients at high risk for colorectal cancer. A prospectively planned analysis of the APC Trial tested the hypothesis that expression of target enzymes in adenomas removed before beginning study treatment would identify individuals at high risk of adenoma development, and/or predict response to Cox-2 inhibition.Methods: Pre-treatment adenomas were examined using immunohistochemistry to assess expression of Cox-2 (high vs. low) and 15-prostaglandin dehydrogenase (15-PGDH, presence vs. loss). The Mantel-Cox test evaluated whether these markers predicted benefit from celecoxib for reduction of adenoma detection.Results: Patients whose pre-treatment adenomas demonstrated elevated Cox-2 achieved the greatest adenoma reduction with celecoxib treatment [RR, 0.37; 95% confidence interval (CI), 0.22-0.61; P = 0.0001]. This reduction was less in the low Cox-2 category (RR, 0.64; 95% CI, 0.56-0.73). Patients whose pre-treatment adenomas showed 15-PGDH loss had a similar treatment-associated reduction in adenoma detection (RR, 0.60; 95% CI, 0.52-0.69; P < 0.0001). In contrast, patients with intact tumor 15-PGDH expression did not significantly benefit from celecoxib (RR, 0.73; 95% CI, 0.47-1.12; P = 0.15). However, subset analysis suggested that this lack of response to celecoxib was confined to those patients with 15-PGDH intact tumors who were also using cardioprotective aspirin.Conclusions: The expression of Cox-2 and 15-PGDH in pre-treatment adenomas provides predictive information in patients treated with celecoxib for prevention of colorectal adenomas.Impact: The results of this study show that Cox-2 and 15-PGDH are characteristics of colorectal adenomas that may be used to predict nonsteroidal anti-inflammatory drug chemoprevention efficacy. Cancer Epidemiol Biomarkers Prev; 27(7); 728-36. ©2018 AACR.

PMID:
29769213
PMCID:
PMC6519921
DOI:
10.1158/1055-9965.EPI-17-0573
[Indexed for MEDLINE]
Free PMC Article

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