title: Second-line oxaliplatin, folinic acid, and fluorouracil versus folinic acid and fluorouracil alone for gemcitabine-refractory pancreatic cancer: outcomes from the CONKO-003 trial.
abstract: OBJECTIVE
  To assess the efficacy of a second-line regimen of oxaliplatin and folinic acid-modulated fluorouracil in patients with advanced pancreatic cancer who have experienced progression while receiving gemcitabine monotherapy.
  
  
  METHODS
  A randomized, open-label, phase III study was conducted in 16 institutions throughout Germany. Recruitment ran from January 2004 until May 2007, and the last follow-up concluded in December 2012. Overall, 168 patients age 18 years or older who experienced disease progression during first-line gemcitabine therapy were randomly assigned to folinic acid and fluorouracil (FF) or oxaliplatin and FF (OFF). Patients were stratified according to the presence of metastases, duration of first-line therapy, and Karnofsky performance status.
  
  
  RESULTS
  Median follow-up was 54.1 months, and 160 patients were eligible for the primary analysis. The median overall survival in the OFF group (5.9 months; 95% CI, 4.1 to 7.4) versus the FF group (3.3 months; 95% CI, 2.7 to 4.0) was significantly improved (hazard ratio [HR], 0.66; 95% CI, 0.48 to 0.91; log-rank P = .010). Time to progression with OFF (2.9 months; 95% CI, 2.4 to 3.2) versus FF (2.0 months; 95% CI, 1.6 to 2.3) was significantly extended also (HR, 0.68; 95% CI, 0.50 to 0.94; log-rank P = .019). Rates of adverse events were similar between treatment arms, with the exception of grades 1 to 2 neurotoxicity, which were reported in 29 patients (38.2%) and six patients (7.1%) in the OFF and FF groups, respectively (P < .001).
  
  
  CONCLUSIONS
  Second-line OFF significantly extended the duration of overall survival when compared with FF alone in patients with advanced gemcitabine-refractory pancreatic cancer.
authors: Helmut Oettle, Hanno Riess, Jens M. Stieler, Sven Bischoff, Marianne Sinn, Bernd Dörken, and Uwe Pelzer, Charitě Universitätsmedizin; Ingo Schwaner, Clinical Center, Berlin; Helmut Oettle, Clinical Center, Friedrichschafen; Gerhard Heil, Clinical Center, Lüdenscheid; Jörg Seraphin, Clinical Center, Northeim; Martin Görner, Clinical Center, Bielefeld; Matthias Mölle, Clinical Center, Dresden; Tim F. Greten, Hannover Medical School, Hannover; and Volker Lakner, Clinical Center, Rostock, Germany. helmut.oettle@charite.de.
authors: Helmut
authors: H
authors: Oettle
authors: Helmut Oettle, Hanno Riess, Jens M. Stieler, Sven Bischoff, Marianne Sinn, Bernd Dörken, and Uwe Pelzer, Charitě Universitätsmedizin; Ingo Schwaner, Clinical Center, Berlin; Helmut Oettle, Clinical Center, Friedrichschafen; Gerhard Heil, Clinical Center, Lüdenscheid; Jörg Seraphin, Clinical Center, Northeim; Martin Görner, Clinical Center, Bielefeld; Matthias Mölle, Clinical Center, Dresden; Tim F. Greten, Hannover Medical School, Hannover; and Volker Lakner, Clinical Center, Rostock, Germany.
authors: Hanno
authors: H
authors: Riess
authors: Helmut Oettle, Hanno Riess, Jens M. Stieler, Sven Bischoff, Marianne Sinn, Bernd Dörken, and Uwe Pelzer, Charitě Universitätsmedizin; Ingo Schwaner, Clinical Center, Berlin; Helmut Oettle, Clinical Center, Friedrichschafen; Gerhard Heil, Clinical Center, Lüdenscheid; Jörg Seraphin, Clinical Center, Northeim; Martin Görner, Clinical Center, Bielefeld; Matthias Mölle, Clinical Center, Dresden; Tim F. Greten, Hannover Medical School, Hannover; and Volker Lakner, Clinical Center, Rostock, Germany.
authors: Jens M
authors: JM
authors: Stieler
authors: Helmut Oettle, Hanno Riess, Jens M. Stieler, Sven Bischoff, Marianne Sinn, Bernd Dörken, and Uwe Pelzer, Charitě Universitätsmedizin; Ingo Schwaner, Clinical Center, Berlin; Helmut Oettle, Clinical Center, Friedrichschafen; Gerhard Heil, Clinical Center, Lüdenscheid; Jörg Seraphin, Clinical Center, Northeim; Martin Görner, Clinical Center, Bielefeld; Matthias Mölle, Clinical Center, Dresden; Tim F. Greten, Hannover Medical School, Hannover; and Volker Lakner, Clinical Center, Rostock, Germany.
authors: Gerhard
authors: G
authors: Heil
authors: Helmut Oettle, Hanno Riess, Jens M. Stieler, Sven Bischoff, Marianne Sinn, Bernd Dörken, and Uwe Pelzer, Charitě Universitätsmedizin; Ingo Schwaner, Clinical Center, Berlin; Helmut Oettle, Clinical Center, Friedrichschafen; Gerhard Heil, Clinical Center, Lüdenscheid; Jörg Seraphin, Clinical Center, Northeim; Martin Görner, Clinical Center, Bielefeld; Matthias Mölle, Clinical Center, Dresden; Tim F. Greten, Hannover Medical School, Hannover; and Volker Lakner, Clinical Center, Rostock, Germany.
authors: Ingo
authors: I
authors: Schwaner
authors: Helmut Oettle, Hanno Riess, Jens M. Stieler, Sven Bischoff, Marianne Sinn, Bernd Dörken, and Uwe Pelzer, Charitě Universitätsmedizin; Ingo Schwaner, Clinical Center, Berlin; Helmut Oettle, Clinical Center, Friedrichschafen; Gerhard Heil, Clinical Center, Lüdenscheid; Jörg Seraphin, Clinical Center, Northeim; Martin Görner, Clinical Center, Bielefeld; Matthias Mölle, Clinical Center, Dresden; Tim F. Greten, Hannover Medical School, Hannover; and Volker Lakner, Clinical Center, Rostock, Germany.
authors: Jörg
authors: J
authors: Seraphin
authors: Helmut Oettle, Hanno Riess, Jens M. Stieler, Sven Bischoff, Marianne Sinn, Bernd Dörken, and Uwe Pelzer, Charitě Universitätsmedizin; Ingo Schwaner, Clinical Center, Berlin; Helmut Oettle, Clinical Center, Friedrichschafen; Gerhard Heil, Clinical Center, Lüdenscheid; Jörg Seraphin, Clinical Center, Northeim; Martin Görner, Clinical Center, Bielefeld; Matthias Mölle, Clinical Center, Dresden; Tim F. Greten, Hannover Medical School, Hannover; and Volker Lakner, Clinical Center, Rostock, Germany.
authors: Martin
authors: M
authors: Görner
authors: Helmut Oettle, Hanno Riess, Jens M. Stieler, Sven Bischoff, Marianne Sinn, Bernd Dörken, and Uwe Pelzer, Charitě Universitätsmedizin; Ingo Schwaner, Clinical Center, Berlin; Helmut Oettle, Clinical Center, Friedrichschafen; Gerhard Heil, Clinical Center, Lüdenscheid; Jörg Seraphin, Clinical Center, Northeim; Martin Görner, Clinical Center, Bielefeld; Matthias Mölle, Clinical Center, Dresden; Tim F. Greten, Hannover Medical School, Hannover; and Volker Lakner, Clinical Center, Rostock, Germany.
authors: Matthias
authors: M
authors: Mölle
authors: Helmut Oettle, Hanno Riess, Jens M. Stieler, Sven Bischoff, Marianne Sinn, Bernd Dörken, and Uwe Pelzer, Charitě Universitätsmedizin; Ingo Schwaner, Clinical Center, Berlin; Helmut Oettle, Clinical Center, Friedrichschafen; Gerhard Heil, Clinical Center, Lüdenscheid; Jörg Seraphin, Clinical Center, Northeim; Martin Görner, Clinical Center, Bielefeld; Matthias Mölle, Clinical Center, Dresden; Tim F. Greten, Hannover Medical School, Hannover; and Volker Lakner, Clinical Center, Rostock, Germany.
authors: Tim F
authors: TF
authors: Greten
authors: Helmut Oettle, Hanno Riess, Jens M. Stieler, Sven Bischoff, Marianne Sinn, Bernd Dörken, and Uwe Pelzer, Charitě Universitätsmedizin; Ingo Schwaner, Clinical Center, Berlin; Helmut Oettle, Clinical Center, Friedrichschafen; Gerhard Heil, Clinical Center, Lüdenscheid; Jörg Seraphin, Clinical Center, Northeim; Martin Görner, Clinical Center, Bielefeld; Matthias Mölle, Clinical Center, Dresden; Tim F. Greten, Hannover Medical School, Hannover; and Volker Lakner, Clinical Center, Rostock, Germany.
authors: Volker
authors: V
authors: Lakner
authors: Helmut Oettle, Hanno Riess, Jens M. Stieler, Sven Bischoff, Marianne Sinn, Bernd Dörken, and Uwe Pelzer, Charitě Universitätsmedizin; Ingo Schwaner, Clinical Center, Berlin; Helmut Oettle, Clinical Center, Friedrichschafen; Gerhard Heil, Clinical Center, Lüdenscheid; Jörg Seraphin, Clinical Center, Northeim; Martin Görner, Clinical Center, Bielefeld; Matthias Mölle, Clinical Center, Dresden; Tim F. Greten, Hannover Medical School, Hannover; and Volker Lakner, Clinical Center, Rostock, Germany.
authors: Sven
authors: S
authors: Bischoff
authors: Helmut Oettle, Hanno Riess, Jens M. Stieler, Sven Bischoff, Marianne Sinn, Bernd Dörken, and Uwe Pelzer, Charitě Universitätsmedizin; Ingo Schwaner, Clinical Center, Berlin; Helmut Oettle, Clinical Center, Friedrichschafen; Gerhard Heil, Clinical Center, Lüdenscheid; Jörg Seraphin, Clinical Center, Northeim; Martin Görner, Clinical Center, Bielefeld; Matthias Mölle, Clinical Center, Dresden; Tim F. Greten, Hannover Medical School, Hannover; and Volker Lakner, Clinical Center, Rostock, Germany.
authors: Marianne
authors: M
authors: Sinn
authors: Helmut Oettle, Hanno Riess, Jens M. Stieler, Sven Bischoff, Marianne Sinn, Bernd Dörken, and Uwe Pelzer, Charitě Universitätsmedizin; Ingo Schwaner, Clinical Center, Berlin; Helmut Oettle, Clinical Center, Friedrichschafen; Gerhard Heil, Clinical Center, Lüdenscheid; Jörg Seraphin, Clinical Center, Northeim; Martin Görner, Clinical Center, Bielefeld; Matthias Mölle, Clinical Center, Dresden; Tim F. Greten, Hannover Medical School, Hannover; and Volker Lakner, Clinical Center, Rostock, Germany.
authors: Bernd
authors: B
authors: Dörken
authors: Helmut Oettle, Hanno Riess, Jens M. Stieler, Sven Bischoff, Marianne Sinn, Bernd Dörken, and Uwe Pelzer, Charitě Universitätsmedizin; Ingo Schwaner, Clinical Center, Berlin; Helmut Oettle, Clinical Center, Friedrichschafen; Gerhard Heil, Clinical Center, Lüdenscheid; Jörg Seraphin, Clinical Center, Northeim; Martin Görner, Clinical Center, Bielefeld; Matthias Mölle, Clinical Center, Dresden; Tim F. Greten, Hannover Medical School, Hannover; and Volker Lakner, Clinical Center, Rostock, Germany.
authors: Uwe
authors: U
authors: Pelzer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D002955:Leucovorin; D005472:Fluorouracil; D000093542:Gemcitabine