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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.