title: Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial.
abstract: BACKGROUND
  The role of adjuvant therapy in resectable pancreatic cancer is still uncertain, and no recommended standard exists.
  
  
  OBJECTIVE
  To test the hypothesis that adjuvant chemotherapy with gemcitabine administered after complete resection of pancreatic cancer improves disease-free survival by 6 months or more.
  
  
  METHODS
  Open, multicenter, randomized controlled phase 3 trial with stratification for resection, tumor, and node status. Conducted from July 1998 to December 2004 in the outpatient setting at 88 academic and community-based oncology centers in Germany and Austria. A total of 368 patients with gross complete (R0 or R1) resection of pancreatic cancer and no prior radiation or chemotherapy were enrolled into 2 groups.
  
  
  METHODS
  Patients received adjuvant chemotherapy with 6 cycles of gemcitabine on days 1, 8, and 15 every 4 weeks (n = 179), or observation ([control] n = 175).
  
  
  METHODS
  Primary end point was disease-free survival, and secondary end points were overall survival, toxicity, and quality of life. Survival analysis was based on all eligible patients (intention-to-treat).
  
  
  RESULTS
  More than 80% of patients had R0 resection. The median number of chemotherapy cycles in the gemcitabine group was 6 (range, 0-6). Grade 3 or 4 toxicities rarely occurred with no difference in quality of life (by Spitzer index) between groups. During median follow-up of 53 months, 133 patients (74%) in the gemcitabine group and 161 patients (92%) in the control group developed recurrent disease. Median disease-free survival was 13.4 months in the gemcitabine group (95% confidence interval, 11.4-15.3) and 6.9 months in the control group (95% confidence interval, 6.1-7.8; P<.001, log-rank). Estimated disease-free survival at 3 and 5 years was 23.5% and 16.5% in the gemcitabine group, and 7.5% and 5.5% in the control group, respectively. Subgroup analyses showed that the effect of gemcitabine on disease-free survival was significant in patients with either R0 or R1 resection. There was no difference in overall survival between the gemcitabine group (median, 22.1 months; 95% confidence interval, 18.4-25.8; estimated survival, 34% at 3 years and 22.5% at 5 years) and the control group (median, 20.2 months; 95% confidence interval, 17-23.4; estimated survival, 20.5% at 3 years and 11.5% at 5 years; P = .06, log-rank).
  
  
  CONCLUSIONS
  Postoperative gemcitabine significantly delayed the development of recurrent disease after complete resection of pancreatic cancer compared with observation alone. These results support the use of gemcitabine as adjuvant chemotherapy in resectable carcinoma of the pancreas.
  
  
  BACKGROUND
  isrctn.org Identifier: ISRCTN34802808.
authors.affiliation: Department of Medical Oncology and Hematology, Charité School of Medicine, Campus Virchow-Klinikum, Berlin, Germany. helmut.oettle@charite.de
authors.forename: Helmut
authors.initials: H
authors.lastname: Oettle
authors.forename: Stefan
authors.initials: S
authors.lastname: Post
authors.forename: Peter
authors.initials: P
authors.lastname: Neuhaus
authors.forename: Klaus
authors.initials: K
authors.lastname: Gellert
authors.forename: Jan
authors.initials: J
authors.lastname: Langrehr
authors.forename: Karsten
authors.initials: K
authors.lastname: Ridwelski
authors.forename: Harald
authors.initials: H
authors.lastname: Schramm
authors.forename: Joerg
authors.initials: J
authors.lastname: Fahlke
authors.forename: Carl
authors.initials: C
authors.lastname: Zuelke
authors.forename: Christof
authors.initials: C
authors.lastname: Burkart
authors.forename: Klaus
authors.initials: K
authors.lastname: Gutberlet
authors.forename: Erika
authors.initials: E
authors.lastname: Kettner
authors.forename: Harald
authors.initials: H
authors.lastname: Schmalenberg
authors.forename: Karin
authors.initials: K
authors.lastname: Weigang-Koehler
authors.forename: Wolf-Otto
authors.initials: WO
authors.lastname: Bechstein
authors.forename: Marco
authors.initials: M
authors.lastname: Niedergethmann
authors.forename: Ingo
authors.initials: I
authors.lastname: Schmidt-Wolf
authors.forename: Lars
authors.initials: L
authors.lastname: Roll
authors.forename: Bernd
authors.initials: B
authors.lastname: Doerken
authors.forename: Hanno
authors.initials: H
authors.lastname: Riess
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000601:surgery*; D011788:Quality of Life; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine