Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial

JAMA. 2008 Mar 5;299(9):1019-26. doi: 10.1001/jama.299.9.1019.

Abstract

Context: Among patients with locally advanced metastatic pancreatic adenocarcinoma, gemcitabine has been shown to improve outcomes compared with fluorouracil.

Objective: To determine if the addition of gemcitabine to adjuvant fluorouracil chemoradiation (chemotherapy plus radiation) improves survival for patients with resected pancreatic adenocarcinoma.

Design, setting, and participants: Randomized controlled phase 3 trial of patients with complete gross total resection of pancreatic adenocarcinoma and no prior radiation or chemotherapy enrolled between July 1998 and July 2002 with follow-up through August 18, 2006, at 164 US and Canadian institutions.

Intervention: Chemotherapy with either fluorouracil (continuous infusion of 250 mg/m2 per day; n = 230) or gemcitabine (30-minute infusion of 1000 mg/m2 once per week; n = 221) for 3 weeks prior to chemoradiation therapy and for 12 weeks after chemoradiation therapy. Chemoradiation with a continuous infusion of fluorouracil (250 mg/m2 per day) was the same for all patients (50.4 Gy).

Main outcome measures: Survival for all patients and survival for patients with pancreatic head tumors were the primary end points. Secondary end points included toxicity.

Results: A total of 451 patients were randomized, eligible, and analyzable. Patients with pancreatic head tumors (n = 388) had a median survival of 20.5 months and a 3-year survival of 31% in the gemcitabine group vs a median survival of 16.9 months and a 3-year survival of 22% in the fluorouracil group (hazard ratio, 0.82 [95% confidence interval, 0.65-1.03]; P = .09). The treatment effect was strengthened on multivariate analysis (hazard ratio, 0.80 [95% confidence interval, 0.63-1.00]; P = .05). Grade 4 hematologic toxicity was 1% in the fluorouracil group and 14% in the gemcitabine group (P < .001) without a difference in febrile neutropenia or infection. There were no differences in the ability to complete chemotherapy or radiation therapy (>85%).

Conclusions: The addition of gemcitabine to adjuvant fluorouracil-based chemoradiation was associated with a survival benefit for patients with resected pancreatic cancer, although this improvement was not statistically significant.

Trial registration: clinicaltrials.gov Identifier: NCT00003216.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / radiotherapy
  • Adenocarcinoma / surgery
  • Adult
  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Combined Modality Therapy
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / therapeutic use
  • Female
  • Fluorouracil / therapeutic use*
  • Gemcitabine
  • Humans
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / radiotherapy
  • Pancreatic Neoplasms / surgery
  • Survival Analysis

Substances

  • Antimetabolites, Antineoplastic
  • Deoxycytidine
  • Fluorouracil
  • Gemcitabine

Associated data

  • ClinicalTrials.gov/NCT00003216