title: Gemcitabine plus cisplatin versus chemoradiotherapy in locally advanced biliary tract cancer: Fédération Francophone de Cancérologie Digestive 9902 phase II randomised study.
abstract: BACKGROUND
  Chemoradiotherapy (CHRT) is often advocated for locally-advanced biliary tract cancer (LABTC). However there was not comparative study with chemotherapy alone (CH).
  
  
  METHODS
  Patients with hilar or extrahepatic non-metastatic, LABTC could be included in this phase II trial. The inclusion criteria required World Health Organisation (WHO) performance status ⩽ 2, bilirubinemia ⩽ 50 μM/L after biliary drainage if necessary, and possibility of external radiotherapy. Fluorouracil (5 FU) infusion and cisplatin, were given in association to radiotherapy (50 Gy) in the CHRT arm. Gemcitabine+oxaliplatin (GEMOX) was planned for 6 months in the CH arm. End-points were progression-free survival (PFS), overall survival (OS), toxicity and rate of biliary complications.
  
  
  RESULTS
  The trial was closed before completion due to slow recruitment. Eighteen and 16 patients were included in the CHRT and CH arms, respectively. Median follow up was 27.9 months (± 2.8). Grade III-IV toxicities were mostly haematological (23% and 25%), and gastrointestinal (11% and 6%), in the CHRT and CH arm, respectively. Biliary complications occurred in 28% of patients in the CHRT arm and 44% of patients in the CH arm (risk ratio (RR): 1.60 [0.65-3.92]). Median PFS was 5.8 months in the CHRT group and 11.0 months in the CH group (hazard ratio (HR): 0.65 [0.32-1.33]). Median OS was 13.5 months in the CHRT group and 19.9 months in the CH group (HR: 0.69 [0.31-1.55]).
  
  
  CONCLUSIONS
  Combination of gemcitabine plus cisplatin seems to be at least as efficient as chemoradiotherapy (50 Gy plus 5 FU and cisplatin) in LABTC.
authors.affiliation: Department of Gastroenterology and Digestive Oncology, University Hospital of St Etienne, University Jean Monnet, LINA EA 4624, France. Electronic address: j.marc.phelip@chu-st-etienne.fr.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Phelip
authors.affiliation: Radiotherapy Department, University Hospital Haut Lévêque Bordeaux, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Vendrely
authors.affiliation: Department of Gastroenterology, University Hospital Le Bocage, Dijon, France.
authors.forename: Florian
authors.initials: F
authors.lastname: Rostain
authors.affiliation: Fédération Francophone de Cancérologie Digestive, Dijon, France; Université de Lyon, F-69000 Lyon, France; Université Lyon 1, CNRS, UMR5558, Laboratoire de Biométrie et Biologie Evolutive, F-69622 Villeurbanne, France; Hospices Civils de Lyon, Service de Biostatistique, F-69003 Lyon, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Subtil
authors.affiliation: Department of Gastroenterology, University Hospital Le Bocage, Dijon, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Jouve
authors.affiliation: Department of Gastroenterology, University Hospital North, Marseille, France.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Gasmi
authors.affiliation: Oncology Department, University Hospital, Rouen, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Michel
authors.affiliation: Fédération Francophone de Cancérologie Digestive, Dijon, France; Université de Lyon, F-69000 Lyon, France; Université Lyon 1, CNRS, UMR5558, Laboratoire de Biométrie et Biologie Evolutive, F-69622 Villeurbanne, France; Hospices Civils de Lyon, Service de Biostatistique, F-69003 Lyon, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Le Malicot
authors.affiliation: Oncology Department, University Hospital Saint-André, Bordeaux, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Smith
authors.affiliation: Department of Gastroenterology and Digestive Oncology, University Hospital La Timone, Marseille, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Seitz
authors.affiliation: Department of Gastroenterology, Hospital of Charleville-Mezieres, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Fauchart
authors.affiliation: Radiotherapy, Boulogne, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Martin
authors.affiliation: Oncology Department, René Gauducheau Center, St Herblain, France.
authors.forename: Jaafar
authors.initials: J
authors.lastname: Bennouna
authors.affiliation: Hospital of Tarbes, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Morin
authors.affiliation: Oncology Department, Hospital of Valenciennes, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bonnet
authors.affiliation: Radiotherapy Department, Center Georges-François Leclerc, Dijon, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Maingon
authors.affiliation: Department of Gastroenterology, University Hospital Le Bocage, Dijon, France; Fédération Francophone de Cancérologie Digestive, Dijon, France; Université de Lyon, F-69000 Lyon, France; Université Lyon 1, CNRS, UMR5558, Laboratoire de Biométrie et Biologie Evolutive, F-69622 Villeurbanne, France; Hospices Civils de Lyon, Service de Biostatistique, F-69003 Lyon, France.
authors.forename: Côme
authors.initials: C
authors.lastname: Lepage
authors.affiliation: Department of Medical Oncology, University Hospital Amiens, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Chauffert
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001661:Biliary Tract Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine
keywords: Biliary tract cancer; Chemoradiotherapy; Cisplatin; Fluorouracil; Gemcitabine; Oxaliplatin