title: FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer.
abstract: BACKGROUND
  Data are lacking on the efficacy and safety of a combination chemotherapy regimen consisting of oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) as compared with gemcitabine as first-line therapy in patients with metastatic pancreatic cancer.
  
  
  METHODS
  We randomly assigned 342 patients with an Eastern Cooperative Oncology Group performance status score of 0 or 1 (on a scale of 0 to 5, with higher scores indicating a greater severity of illness) to receive FOLFIRINOX (oxaliplatin, 85 mg per square meter of body-surface area; irinotecan, 180 mg per square meter; leucovorin, 400 mg per square meter; and fluorouracil, 400 mg per square meter given as a bolus followed by 2400 mg per square meter given as a 46-hour continuous infusion, every 2 weeks) or gemcitabine at a dose of 1000 mg per square meter weekly for 7 of 8 weeks and then weekly for 3 of 4 weeks. Six months of chemotherapy were recommended in both groups in patients who had a response. The primary end point was overall survival.
  
  
  RESULTS
  The median overall survival was 11.1 months in the FOLFIRINOX group as compared with 6.8 months in the gemcitabine group (hazard ratio for death, 0.57; 95% confidence interval [CI], 0.45 to 0.73; P<0.001). Median progression-free survival was 6.4 months in the FOLFIRINOX group and 3.3 months in the gemcitabine group (hazard ratio for disease progression, 0.47; 95% CI, 0.37 to 0.59; P<0.001). The objective response rate was 31.6% in the FOLFIRINOX group versus 9.4% in the gemcitabine group (P<0.001). More adverse events were noted in the FOLFIRINOX group; 5.4% of patients in this group had febrile neutropenia. At 6 months, 31% of the patients in the FOLFIRINOX group had a definitive degradation of the quality of life versus 66% in the gemcitabine group (hazard ratio, 0.47; 95% CI, 0.30 to 0.70; P<0.001).
  
  
  CONCLUSIONS
  As compared with gemcitabine, FOLFIRINOX was associated with a survival advantage and had increased toxicity. FOLFIRINOX is an option for the treatment of patients with metastatic pancreatic cancer and good performance status. (Funded by the French government and others; ClinicalTrials.gov number, NCT00112658.).
authors.affiliation: Nancy University and Department of Medical Oncology, Centre Alexis Vautrin, Nancy, France. t.conroy@nancy.fnclcc.fr
authors.forename: Thierry
authors.initials: T
authors.lastname: Conroy
authors.forename: Françoise
authors.initials: F
authors.lastname: Desseigne
authors.forename: Marc
authors.initials: M
authors.lastname: Ychou
authors.forename: Olivier
authors.initials: O
authors.lastname: Bouché
authors.forename: Rosine
authors.initials: R
authors.lastname: Guimbaud
authors.forename: Yves
authors.initials: Y
authors.lastname: Bécouarn
authors.forename: Antoine
authors.initials: A
authors.lastname: Adenis
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Raoul
authors.forename: Sophie
authors.initials: S
authors.lastname: Gourgou-Bourgade
authors.forename: Christelle
authors.initials: C
authors.lastname: de la Fouchardière
authors.forename: Jaafar
authors.initials: J
authors.lastname: Bennouna
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Bachet
authors.forename: Faiza
authors.initials: F
authors.lastname: Khemissa-Akouz
authors.forename: Denis
authors.initials: D
authors.lastname: Péré-Vergé
authors.forename: Catherine
authors.initials: C
authors.lastname: Delbaldo
authors.forename: Eric
authors.initials: E
authors.lastname: Assenat
authors.forename: Bruno
authors.initials: B
authors.lastname: Chauffert
authors.forename: Pierre
authors.initials: P
authors.lastname: Michel
authors.forename: Christine
authors.initials: C
authors.lastname: Montoto-Grillot
authors.forename: Michel
authors.initials: M
authors.lastname: Ducreux
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016016:Proportional Hazards Models; D011788:Quality of Life; D012720:Severity of Illness Index; D016019:Survival Analysis; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin; D000093542:Gemcitabine