title: Gemcitabine versus cisplatin, epirubicin, fluorouracil, and gemcitabine in advanced pancreatic cancer: a randomised controlled multicentre phase III trial.
abstract: BACKGROUND
  Patients with advanced pancreatic adenocarcinoma have a poor response, progression-free survival, and overall survival with standard treatment. We aimed to assess whether a four-drug regimen could improve 4 month progression-free survival compared with gemcitabine alone.
  
  
  METHODS
  In a randomised multicentre phase III trial, 52 patients were randomly assigned to 40 mg/m2 cisplatin and 40 mg/m2 epirubicin both given on day 1, 600 mg/m2 gemcitabine given intravenously over 1 h on days 1 and 8, and 200 mg/m2 fluorouracil a day given by continuous infusion on days 1-28 of a 4-week cycle (PEFG regimen), and 47 were assigned to 1000 mg/m2 gemcitabine given intravenously over 30 min once a week for 7 of 8 consecutive weeks in cycle 1 and for 3 of 4 weeks thereafter. The primary endpoint was 4-month progression-free survival. Secondary endpoints were overall survival, objective response, safety, and quality of life. Analyses were by intention to treat.
  
  
  RESULTS
  51 patients assigned PEFG and 46 assigned gemcitabine alone had disease progression. 49 patients in the PEFG group and 46 in the gemcitabine group died from progressive disease. More patients allocated PEFG than gemcitabine alone were alive without progressive disease at 4 months (60% [95% CI 46-72] vs 28% [17-42]; hazard ratio [HR] 0.46 [0.26-0.79]). 1-year overall survival in the PEFG group was 38.5% (25.3-51.7) and in the gemcitabine group was 21.3% (9.6-33.0; HR 0.68 [0.42-1.09]). More patients assigned PEFG showed disease response than did those assigned gemcitabine (38.5% [25.3-51.7] vs 8.5% [0.5-16.5]; odds ratio 6.60 [2.11-20.60], p=0.0008). More patients in the PEFG group had grade 3-4 neutropenia and thrombocytopenia than in the gemcitabine group (p<0.0001).
  
  
  CONCLUSIONS
  The PEFG regimen could be considered for treatment of advanced pancreatic adenocarcinoma.
authors.affiliation: Department of Radiochemotherapy, S Raffaele H Scientific Institute, Milan, Italy. reni.michele@hsr.it
authors.forename: Michele
authors.initials: M
authors.lastname: Reni
authors.forename: Stefano
authors.initials: S
authors.lastname: Cordio
authors.forename: Carlo
authors.initials: C
authors.lastname: Milandri
authors.forename: Paolo
authors.initials: P
authors.lastname: Passoni
authors.forename: Elisa
authors.initials: E
authors.lastname: Bonetto
authors.forename: Cristina
authors.initials: C
authors.lastname: Oliani
authors.forename: Gabriele
authors.initials: G
authors.lastname: Luppi
authors.forename: Roberto
authors.initials: R
authors.lastname: Nicoletti
authors.forename: Laura
authors.initials: L
authors.lastname: Galli
authors.forename: Roberto
authors.initials: R
authors.lastname: Bordonaro
authors.forename: Alessandro
authors.initials: A
authors.lastname: Passardi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Zerbi
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Balzano
authors.forename: Luca
authors.initials: L
authors.lastname: Aldrighetti
authors.forename: Carlo
authors.initials: C
authors.lastname: Staudacher
authors.forename: Eugenio
authors.initials: E
authors.lastname: Villa
authors.forename: Valerio
authors.initials: V
authors.lastname: Di Carlo
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D007558:Italy; D008297:Male; D008875:Middle Aged; D010166:Palliative Care; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D015251:Epirubicin; D002945:Cisplatin; D005472:Fluorouracil; D000093542:Gemcitabine