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.
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. TumorCOX-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.
Authors: Robert W Haile; Ji Min Yochim; Victoria K Cortessis; Jesse Lin; A Joan Levine; Anh Diep; Kathy Danenberg; Peter Danenberg Journal: Clin Colorectal Cancer Date: 2005-03 Impact factor: 4.481
Authors: R Masunaga; H Kohno; D K Dhar; S Ohno; M Shibakita; S Kinugasa; H Yoshimura; M Tachibana; H Kubota; N Nagasue Journal: Clin Cancer Res Date: 2000-10 Impact factor: 12.531
Authors: Rachel S Midgley; Christopher C McConkey; Elaine C Johnstone; Janet A Dunn; Justine L Smith; Simon A Grumett; Patrick Julier; Claire Iveson; Yoko Yanagisawa; Bryan Warren; Michael J Langman; David J Kerr Journal: J Clin Oncol Date: 2010-09-13 Impact factor: 44.544
Authors: Bassel F El-Rayes; Mark M Zalupski; Stephanie G Manza; Barbara Rusin; Ann Marie Ferris; Ulka Vaishampayan; Lance K Heilbrun; Raghu Venkatramanamoorthy; Anthony F Shields; Philip A Philip Journal: Cancer Chemother Pharmacol Date: 2007-04-12 Impact factor: 3.333
Authors: Lisa Y Pang; Sally A Argyle; Ayako Kamida; Katherine O'Neill Morrison; David J Argyle Journal: BMC Vet Res Date: 2014-09-05 Impact factor: 2.741