title: 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.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Clinica di Oncologia Medica, Universita' Politecnica delle Marche, Azienda ospedaliera Ospedali Riuniti Umberto I, Lancisi, Salesi, Ancona, Italy. cascinu@yahoo.com
authors.forename: Stefano
authors.initials: S
authors.lastname: Cascinu
authors.forename: Mario
authors.initials: M
authors.lastname: Scartozzi
authors.forename: Giovanna
authors.initials: G
authors.lastname: Carbonari
authors.forename: Chiara
authors.initials: C
authors.lastname: Pierantoni
authors.forename: Lorena
authors.initials: L
authors.lastname: Verdecchia
authors.forename: Cinzia
authors.initials: C
authors.lastname: Mariani
authors.forename: Michela
authors.initials: M
authors.lastname: Squadroni
authors.forename: Stefania
authors.initials: S
authors.lastname: Antognoli
authors.forename: Rosa Rita
authors.initials: RR
authors.lastname: Silva
authors.forename: Riccardo
authors.initials: R
authors.lastname: Giampieri
authors.forename: Rossana
authors.initials: R
authors.lastname: Berardi
mesh_terms: D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity; D000068579:Celecoxib; D051546:Cyclooxygenase 2 / Q000235:genetics*; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use* / Q000633:toxicity; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics*; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D018579:Patient Selection; D011237:Predictive Value of Tests; D011720:Pyrazoles / Q000627:therapeutic use; D013449:Sulfonamides / Q000627:therapeutic use; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016328:NF-kappa B; D009944:Organoplatinum Compounds; D011720:Pyrazoles; D013449:Sulfonamides; D000077150:Oxaliplatin; D003841:Deoxycytidine; D051546:Cyclooxygenase 2; D000068579:Celecoxib; D000093542:Gemcitabine