title: Fluorouracil-based chemoradiation with either gemcitabine or fluorouracil chemotherapy after resection of pancreatic adenocarcinoma: 5-year analysis of the U.S. Intergroup/RTOG 9704 phase III trial.
abstract: BACKGROUND
  The impact of the addition of gemcitabine to 5-fluorouracil (5-FU) chemoradiation (CRT) on 5-year overall survival (OS) in resected pancreatic adenocarcinoma are presented with updated results of a phase III trial.
  
  
  METHODS
  After resection of pancreatic adenocarcinoma, patients were randomized to pre- and post-CRT 5-FU versus pre- and post-CRT gemcitabine. 5-FU was provided continuously at 250 mg/m(2)/day, and gemcitabine was provided at 1000 mg/m(2) weekly. Both were provided over 3 weeks before and 12 weeks after CRT. CRT was provided at 50.4 Gy with continuously provided 5-FU. The primary end point was survival for all patients and for patients with tumor of the pancreatic head.
  
  
  RESULTS
  Four hundred fifty-one patients were eligible. Univariate analysis showed no difference in OS. Pancreatic head tumor patients (n = 388) had a median survival and 5-year OS of 20.5 months and 22% with gemcitabine versus 17.1 months and 18% with 5-FU. On multivariate analysis, patients on the gemcitabine arm with pancreatic head tumors experienced a trend toward improved OS (P = 0.08). First site of relapse local recurrence in 28% of patients versus distant relapse in 73%.
  
  
  CONCLUSIONS
  The sequencing of 5-FU CRT with gemcitabine as done in this trial is not associated with a statistically significant improvement in OS. Despite local recurrence being approximately half of that reported in previous adjuvant trials, distant disease relapse still occurs in ≥ 70% of patients. These findings serve as the basis for the recently activated EORTC/U.S. Intergroup RTOG 0848 phase III adjuvant trial evaluating the impact of CRT after completion of a full course of gemcitabine.
authors.affiliation: Department of Radiation Oncology, University of Maryland, Baltimore, MD, USA, wregine@umm.edu
authors.forename: William F
authors.initials: WF
authors.lastname: Regine
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Winter
authors.forename: Ross
authors.initials: R
authors.lastname: Abrams
authors.forename: Howard
authors.initials: H
authors.lastname: Safran
authors.forename: John P
authors.initials: JP
authors.lastname: Hoffman
authors.forename: Andre
authors.initials: A
authors.lastname: Konski
authors.forename: Al B
authors.initials: AB
authors.lastname: Benson
authors.forename: John S
authors.initials: JS
authors.lastname: Macdonald
authors.forename: Tyvin A
authors.initials: TA
authors.lastname: Rich
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Willett
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015331:Cohort Studies; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D011446:Prospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D005472:Fluorouracil; D000093542:Gemcitabine