Association between COX-2 expression and effectiveness of COX-2 inhibitors in a phase II trial in patients with metastatic colorectal adenocarcinoma.
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/m(2) over 30 min i.v. on days 1 and 8, capecitabine 1,000 mg/m(2) 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.