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.
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.
Cascinu
Stefano
S
Clinica di Oncologia Medica, Universita' Politecnica delle Marche, Azienda ospedaliera Ospedali Riuniti Umberto I, Lancisi, Salesi, Ancona, Italy. cascinu@yahoo.com
Scartozzi
Mario
M
Carbonari
Giovanna
G
Pierantoni
Chiara
C
Verdecchia
Lorena
L
Mariani
Cinzia
C
Squadroni
Michela
M
Antognoli
Stefania
S
Silva
Rosa Rita
RR
Giampieri
Riccardo
R
Berardi
Rossana
R
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
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