title: Gemcitabine plus celecoxib in patients with advanced or metastatic pancreatic adenocarcinoma: results of a phase II trial.
abstract: OBJECTIVE
  Cycloxygenase-2 (COX-2) is overexpressed in pancreatic tumors where it may be involved in inflammation, carcinogenesis, and the regulation of neoangiogenesis. The purpose of this trial was to evaluate the combination of intravenous gemcitabine with selective COX-2 inhibitor, celecoxib for effect on survival, disease progression, and tolerability in patients with advanced pancreatic cancer. In addition, limited pharmacokinetic and pharmacodynamic analyses were preformed.
  
  
  METHODS
  Eligible patients included those with locally advanced or metastatic pancreatic cancer with no prior chemotherapy and ECOG performance status 0-2. The treatment consisted of intravenous gemcitabine 1000 mg/m weekly x 7 weeks and concurrent daily oral celecoxib 400 mg orally twice a day. Daily oral low-dose aspirin 81 mg was administered throughout the study as a precaution for increased risk of thrombotic events. Those with stable or responsive disease were continued on intravenous gemcitabine 1000 mg/m weekly x 3 weeks and concurrent oral celecoxib.
  
  
  RESULTS
  Twenty five patients have been enrolled at 3 centers. Five patients had locally advanced cancer; 20 had metastatic disease. The most common grade 3/4 hematological toxicities were neutropenia (32%) and anemia (20%). Four patients (17%) had partial response and 7 (35%) demonstrated stable disease. The estimated 12-month survival rate was 15%, which did not reach the predetermined efficacy end point. There was a trend suggestive of correlation between a decrease in serum vascular endothelial growth factor and patient survival.
  
  
  CONCLUSIONS
  The addition of celecoxib to gemcitabine therapy did not demonstrate significant improvement in measured clinical outcomes, in patients with advanced pancreatic cancer. Higher doses of celecoxib may be needed to observe significant antitumor activity.
authors.affiliation: University of Arizona Health Sciences Center and Arizona Cancer Center, Tucson, AZ 85724, USA. tdragovich@azcc.arizona.edu
authors.forename: Tomislav
authors.initials: T
authors.lastname: Dragovich
authors.forename: Howard
authors.initials: H
authors.lastname: Burris
authors.forename: Patrick
authors.initials: P
authors.lastname: Loehrer
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Von Hoff
authors.forename: Sherry
authors.initials: S
authors.lastname: Chow
authors.forename: Steven
authors.initials: S
authors.lastname: Stratton
authors.forename: Sylvan
authors.initials: S
authors.lastname: Green
authors.forename: Yrma
authors.initials: Y
authors.lastname: Obregon
authors.forename: Irene
authors.initials: I
authors.lastname: Alvarez
authors.forename: Michael
authors.initials: M
authors.lastname: Gordon
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000068579:Celecoxib; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D016019:Survival Analysis; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000097:blood; D000093542:Gemcitabine
chemical_list: D011720:Pyrazoles; D013449:Sulfonamides; D042461:Vascular Endothelial Growth Factor A; D003841:Deoxycytidine; D000068579:Celecoxib; D000093542:Gemcitabine