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

Am J Clin Oncol. 2007 Oct;30(5):526-30. doi: 10.1097/COC.0b013e318054675c.

Abstract

Objective: 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.

Methods: Forty-four patients with histologically or cytologically verified, locally advanced unresectable and/or metastatic pancreatic carcinoma were eligible for the study.

Results: 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.

Conclusion: 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.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • 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
  • Gemcitabine
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • NF-kappa B / genetics*
  • Organoplatinum Compounds / administration & dosage
  • Oxaliplatin
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / enzymology
  • Pancreatic Neoplasms / genetics
  • Patient Selection
  • Predictive Value of Tests
  • Pyrazoles / therapeutic use
  • Sulfonamides / therapeutic use
  • Treatment Outcome

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase 2 Inhibitors
  • NF-kappa B
  • Organoplatinum Compounds
  • Pyrazoles
  • Sulfonamides
  • Oxaliplatin
  • Deoxycytidine
  • Cyclooxygenase 2
  • Celecoxib
  • Gemcitabine