title: Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial.
abstract: BACKGROUND
  Adjuvant fluorouracil has been shown to be of benefit for patients with resected pancreatic cancer. Gemcitabine is known to be the most effective agent in advanced disease as well as an effective agent in patients with resected pancreatic cancer.
  
  
  OBJECTIVE
  To determine whether fluorouracil or gemcitabine is superior in terms of overall survival as adjuvant treatment following resection of pancreatic cancer.
  
  
  METHODS
  The European Study Group for Pancreatic Cancer (ESPAC)-3 trial, an open-label, phase 3, randomized controlled trial conducted in 159 pancreatic cancer centers in Europe, Australasia, Japan, and Canada. Included in ESPAC-3 version 2 were 1088 patients with pancreatic ductal adenocarcinoma who had undergone cancer resection; patients were randomized between July 2000 and January 2007 and underwent at least 2 years of follow-up.
  
  
  METHODS
  Patients received either fluorouracil plus folinic acid (folinic acid, 20 mg/m(2), intravenous bolus injection, followed by fluorouracil, 425 mg/m(2) intravenous bolus injection given 1-5 days every 28 days) (n = 551) or gemcitabine (1000 mg/m(2) intravenous infusion once a week for 3 of every 4 weeks) (n = 537) for 6 months.
  
  
  METHODS
  Primary outcome measure was overall survival; secondary measures were toxicity, progression-free survival, and quality of life.
  
  
  RESULTS
  Final analysis was carried out on an intention-to-treat basis after a median of 34.2 (interquartile range, 27.1-43.4) months' follow-up after 753 deaths (69%). Median survival was 23.0 (95% confidence interval [CI], 21.1-25.0) months for patients treated with fluorouracil plus folinic acid and 23.6 (95% CI, 21.4-26.4) months for those treated with gemcitabine (chi(1)(2) = 0.7; P = .39; hazard ratio, 0.94 [95% CI, 0.81-1.08]). Seventy-seven patients (14%) receiving fluorouracil plus folinic acid had 97 treatment-related serious adverse events, compared with 40 patients (7.5%) receiving gemcitabine, who had 52 events (P < .001). There were no significant differences in either progression-free survival or global quality-of-life scores between the treatment groups.
  
  
  CONCLUSIONS
  Compared with the use of fluorouracil plus folinic acid, gemcitabine did not result in improved overall survival in patients with completely resected pancreatic cancer.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00058201.
authors.affiliation: Liverpool Cancer Research UK Cancer Trials Unit, Cancer Research UK Centre, University of Liverpool, Fifth Floor, UCD Bldg, Daulby Street, Liverpool, L69 3GA, United Kingdom. j.p.neoptolemos@liverpool.ac.uk
authors.forename: John P
authors.initials: JP
authors.lastname: Neoptolemos
authors.forename: Deborah D
authors.initials: DD
authors.lastname: Stocken
authors.forename: Claudio
authors.initials: C
authors.lastname: Bassi
authors.forename: Paula
authors.initials: P
authors.lastname: Ghaneh
authors.forename: David
authors.initials: D
authors.lastname: Cunningham
authors.forename: David
authors.initials: D
authors.lastname: Goldstein
authors.forename: Robert
authors.initials: R
authors.lastname: Padbury
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Moore
authors.forename: Steven
authors.initials: S
authors.lastname: Gallinger
authors.forename: Christophe
authors.initials: C
authors.lastname: Mariette
authors.forename: Moritz N
authors.initials: MN
authors.lastname: Wente
authors.forename: Jakob R
authors.initials: JR
authors.lastname: Izbicki
authors.forename: Helmut
authors.initials: H
authors.lastname: Friess
authors.forename: Markus M
authors.initials: MM
authors.lastname: Lerch
authors.forename: Christos
authors.initials: C
authors.lastname: Dervenis
authors.forename: Attila
authors.initials: A
authors.lastname: Oláh
authors.forename: Giovanni
authors.initials: G
authors.lastname: Butturini
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Doi
authors.forename: Pehr A
authors.initials: PA
authors.lastname: Lind
authors.forename: David
authors.initials: D
authors.lastname: Smith
authors.forename: Juan W
authors.initials: JW
authors.lastname: Valle
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Palmer
authors.forename: John A
authors.initials: JA
authors.lastname: Buckels
authors.forename: Joyce
authors.initials: J
authors.lastname: Thompson
authors.forename: Colin J
authors.initials: CJ
authors.lastname: McKay
authors.forename: Charlotte L
authors.initials: CL
authors.lastname: Rawcliffe
authors.forename: Markus W
authors.initials: MW
authors.lastname: Büchler
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000601:surgery; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018450:Disease Progression; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000601:surgery; D011788:Quality of Life; D016019:Survival Analysis; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D002955:Leucovorin; D005472:Fluorouracil; D000093542:Gemcitabine