COX-2 and NF-KB overexpression is common in pancreatic cancer but does not predict for COX-2 inhibitors activity in combination with gemcitabine and oxaliplatin

• Published in: American journal of clinical oncology Vol. 30; no. 5; p. 526
• Main Authors: Cascinu, Stefano, Scartozzi, Mario, Carbonari, Giovanna, Pierantoni, Chiara, Verdecchia, Lorena, Mariani, Cinzia, Squadroni, Michela, Antognoli, Stefania, Silva, Rosa Rita, Giampieri, Riccardo, Berardi, Rossana
• Format: Journal Article
• Language: English
• Published: United States 01.10.2007
• Subjects: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - toxicity; Celecoxib; Cyclooxygenase 2 - genetics; Cyclooxygenase 2 Inhibitors - therapeutic use; Cyclooxygenase 2 Inhibitors - toxicity; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Male; Middle Aged; NF-kappa B - genetics; Organoplatinum Compounds - administration & dosage; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - enzymology; Pancreatic Neoplasms - genetics; Patient Selection; Predictive Value of Tests; Pyrazoles - therapeutic use; Sulfonamides - therapeutic use; Treatment Outcome
• ISSN: 1537-453X
• DOI: 10.1097/COC.0b013e318054675c

The attempt to improve therapeutic results in pancreatic carcinoma has recently focused on the emerging role of molecular biology. We investigated the role of COX-2 and NF-KB expression in relation to the use of a COX-2 inhibitor (celecoxib) associated to gemcitabine and oxaliplatin in pancreatic cancer. Forty-four patients with histologically or cytologically verified, locally advanced unresectable and/or metastatic pancreatic carcinoma were eligible for the study. Thirty-three patients (75%) assumed celecoxib for all their treatment period. Treatment was repeated every 2 weeks, until there was evidence of disease progression, patient refusal, or unacceptable toxicity. Efficacy was assessed according to tumor response, clinical benefit, and time-related parameters. Five patients had a partial response, 24 had a stable disease, and 15 had a disease progression, for an overall response rate of 11%. Biochemical response rate based on CA 19.9 levels showed 2 complete and 10 partial responses, whereas 31 patients presented no changes of CA 19.9 levels. COX-2 protein expression was found in 30 tumors, while a moderate or weak/absent expression was present in 10 patients. Sixteen tumors showed a strong expression for NF-KB, 4 a moderate expression, and 5 a weak/absent expression. The use of a COX-2 inhibitor does not add any valuable activity to a gemcitabine/oxaliplatin combination, even in patients with COX-2 and NF-KB overexpressing tumors.