title: Pilot study of celecoxib and infusional 5-fluorouracil as second-line treatment for advanced pancreatic carcinoma.
abstract: BACKGROUND
  Cyclooxygenase-2 (COX-2) is up-regulated frequently and may constitute a promising therapeutic target in patients with pancreatic ductal adenocarcinoma (PDAC).
  
  
  METHODS
  Patients with advanced PDAC who had progressive disease after gemcitabine-based chemotherapy were eligible for this pilot study. Treatment was comprised of oral celecoxib (400 mg twice daily) and protracted intravenous (i.v.) infusion 5-fluorouracil (5-FU) (200 mg/m(2) per day), both given continuously for a maximum of 9 treatment months, in the absence of disease progression or unacceptable toxicity. Patients were examined weekly for toxicity and were restaged every 6-8 weeks for tumor assessment.
  
  
  RESULTS
  Seventeen patients entered the study. Asymptomatic transaminase elevation was the most common toxicity and reached NCI-CTC (version 3.0) Grade 3-4 in 4 of 133 treatment weeks. No other hematologic or nonhematologic toxicity > Grade 2 was observed. Four patients discontinued celecoxib due to upper gastrointestinal tract toxicity. Two confirmed partial responses (durations of 23 weeks and 68 weeks, respectively) and 2 patients with stable disease (durations of 10 weeks and 13 weeks, respectively) were observed for an overall response rate of 12% (95% confidence interval, 0-27%) in the intent-to-treat population. A significant decrease (> or = 50%) in serum CA 19.9 levels was observed in 3 of 9 evaluable patients. The median time to disease progression was 8 weeks, and the median overall survival was 15 weeks.
  
  
  CONCLUSIONS
  The combination of oral celecoxib and 5-FU by protracted i.v. infusion was found to be feasible and well tolerated, and was capable of inducing durable objective responses, even in patients with far advanced, gemcitabine-resistant/refractory PDAC. Further exploration of COX-2 inhibitor/fluropyrimidine combinations is warranted.
authors.affiliation: Divisions of Medical Oncology "A" and "C", Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy. milella@ifo.it
authors.forename: Michele
authors.initials: M
authors.lastname: Milella
authors.forename: Alain
authors.initials: A
authors.lastname: Gelibter
authors.forename: Serena
authors.initials: S
authors.lastname: Di Cosimo
authors.forename: Emilio
authors.initials: E
authors.lastname: Bria
authors.forename: Enzo Maria
authors.initials: EM
authors.lastname: Ruggeri
authors.forename: Paolo
authors.initials: P
authors.lastname: Carlini
authors.forename: Paola
authors.initials: P
authors.lastname: Malaguti
authors.forename: Mario
authors.initials: M
authors.lastname: Pellicciotta
authors.forename: Edmondo
authors.initials: E
authors.lastname: Terzoli
authors.forename: Francesco
authors.initials: F
authors.lastname: Cognetti
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002272:Carcinoembryonic Antigen / Q000097:blood / Q000187:drug effects; D000068579:Celecoxib; D018450:Disease Progression; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010865:Pilot Projects; D011720:Pyrazoles; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D002272:Carcinoembryonic Antigen; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib; D005472:Fluorouracil