PT  - JOURNAL ARTICLE
AU  - ALMHANNA, KHALDOUN
AU  - EL-RAYES, BASSEL
AU  - SETHI, SEEMA
AU  - DYSON, GREGORY
AU  - HEILBRUN, LANCE
AU  - PHILIP, PHILIP A
AU  - SARKAR, FAZLUL
TI  - Association Between COX-2 Expression and Effectiveness of COX-2 Inhibitors in a Phase II Trial in Patients with Metastatic Colorectal Adenocarcinoma
DP  - 2012 Aug 01
TA  - Anticancer Research
PG  - 3559--3563
VI  - 32
IP  - 8
4099  - http://ar.iiarjournals.org/content/32/8/3559.short
4100  - http://ar.iiarjournals.org/content/32/8/3559.full
SO  - Anticancer Res2012 Aug 01; 32
AB  - Aim: The role for the cyclooxygenase-2 (COX-2) pathway in colorectal carcinogenesis has been suggested in pre-clinical models. In a previously reported phase II trial, the addition of COX-2 inhibitor celecoxib to irinotecan and capecitabine did not appear to significantly increase the activity of chemotherapy in patients with metastatic colorectal carcinoma (mCRC). We evaluated the COX-2 expression in the available tumors from enrolled patients by immunohistochemistry, as well as its correlation with clinical outcome. Patients and Methods: Fifty-one patients with mCRC were enrolled in the phase II study between June 2002 and November 2005. Patients received a combination of irinotecan 70 mg/m2 over 30 min i.v. on days 1 and 8, capecitabine 1,000 mg/m2 twice per day orally on days 1-14 and the COX-2 inhibitor celecoxib at a daily dose of 800 mg continuously. Cycles were repeated every 21 days. Formalin-fixed paraffin-embedded tumor tissue samples were available for 17 patients enrolled on this study. COX-2 expression was evaluated by immunohistochemistry and was correlated with clinical outcome. Results: In the phase II study, the objective response rate was 41%. The median time to progression was 7.7 months and median survival time was 21.2 months. Tumor COX-2 expression, by immunohistochemistry, was assessed for 17 patients enrolled in the same phase II study. While not statistically significant, the response rate was better for patients in the low COX-2 expression group, while time to progression and overall survival was longer in patients in the high COX-2 expression group. This discrepancy can be partially attributed to the small sample size. Conclusion: In the previously published phase II study, the addition of celecoxib to irinotecan and capecitabine did not appear to significantly increase the activity of chemotherapy. COX-2 expression by immunohistochemistry was neither prognostic nor predictive for response.