title: Second-line chemotherapy for advanced biliary tract cancer after failure of the gemcitabine-platinum combination: A large multicenter study by the Association des Gastro-Entérologues Oncologues.
abstract: BACKGROUND
  Few data are available on second-line chemotherapy (CT2) for advanced biliary tract cancer (ABTC). The aim of this multicenter study was to describe the CT2 regimens used, the response rates, and the outcomes of patients treated with various CT2 regimens.
  
  
  METHODS
  Patients who received CT2 for ABTC at 17 French institutions after the failure of the gemcitabine-platinum combination were retrospectively studied. Progression-free survival (PFS) and overall survival (OS) were estimated with the Kaplan-Meier method. Cox models were used for multivariate analyses.
  
  
  RESULTS
  Among 603 patients who received first-line chemotherapy (CT1) for ABTC, 196 received CT2: 5-fluorouracil (5-FU) and irinotecan (n = 64), 5-FU and oxaliplatin (n = 21), 5-FU and cisplatin (n = 38), 5-FU or capecitabine (n = 40), sunitinib (n = 10), or other various regimens (n = 23). Among the 186 assessable patients, there were 22 partial responses and 70 stabilizations. After a median follow-up of 26.4 months, the median PFS and OS were 3.2 and 6.7 months, respectively. There was no significant difference in PFS or OS between CT2 regimens. Fluoropyrimidine-based doublet chemotherapy was not superior to fluoropyrimidine alone in terms of OS and PFS. In a multivariate analysis, a performance status of 0 to 1, disease control with CT1, and a carbohydrate antigen 19-9 (CA 19-9) level ≤ 400 IU/mL were significantly associated with longer PFS and OS. Grade 3 to 4 toxicity occurred in 32% of the patients.
  
  
  CONCLUSIONS
  CT2 might provide disease control for selected patients with ABTC after the failure of gemcitabine-platinum, but the prognosis remains poor. No particular regimen seems superior to others, and this calls for new treatments. A good performance status, disease control with CT1, and a low level of CA 19-9 were associated with longer survival.
authors.affiliation: Gastroenterology and Digestive Oncology Unit, Cochin Teaching Hospital, Paris, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Brieau
authors.affiliation: Digestive Oncology Unit, La Timone Hospital, Marseille, France.|Faculty of Medicine-Timone, Aix-Marseille University, Marseille, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Dahan
authors.affiliation: Public Health Department, Curie Institute, Paris, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: De Rycke
authors.affiliation: Gastroenterology Unit, Saint Antoine Hospital, Paris, France.
authors.forename: Tarek
authors.initials: T
authors.lastname: Boussaha
authors.affiliation: Gastroenterology Unit, Poitiers Teaching Hospital, Poitiers, France.|Laboratory of Inflammation, Epithelial Tissues, and Cytokines (EA 4331), Poitiers University, Poitiers, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Vasseur
authors.affiliation: Gastroenterology Unit, Poitiers Teaching Hospital, Poitiers, France.|Laboratory of Inflammation, Epithelial Tissues, and Cytokines (EA 4331), Poitiers University, Poitiers, France.
authors.forename: David
authors.initials: D
authors.lastname: Tougeron
authors.affiliation: Gastroenterology Unit, Tours Teaching Hospital, Tours, France.|Faculty of Medicine, Francois Rabelais University, Tours, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Lecomte
authors.affiliation: Gastroenterology and Digestive Oncology Unit, Cochin Teaching Hospital, Paris, France.|Cochin-Port Royal Faculty of Medicine, Paris Descartes University, Paris, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Coriat
authors.affiliation: Gastroenterology Unit, La Pitié Salpêtrière Hospital, Paris, France.|Faculty of Medicine, Pierre and Marie Curie University, Paris, France.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Bachet
authors.affiliation: Gastroenterology and Hepatology Unit, Saint Etienne Teaching Hospital, North Hospital, Saint-Priest-en-Jarez, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Claudez
authors.affiliation: Gastroenterology and Digestive Unit, Georges Pompidou European Hospital, Paris, France.|Paris Descartes University-Sorbonne Paris Cité, Paris, France.
authors.forename: Aziz
authors.initials: A
authors.lastname: Zaanan
authors.affiliation: Gastroenterology Unit, Reims Teaching Hospital, Reims, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Soibinet
authors.affiliation: Gastroenterology Unit, Jean Mermoz Hospital, Lyon, France.
authors.forename: Jérome
authors.initials: J
authors.lastname: Desrame
authors.affiliation: Gastroenterology Unit, Kremlin-Bicêtre Hospital, Le Kremlin-Bicêtre, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Thirot-Bidault
authors.affiliation: Gastroenterology Unit, Amboise Paré Hospital, Boulogne-Billancourt, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Trouilloud
authors.affiliation: Gastroenterology Unit, Avicenne Hospital, Bobigny, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Mary
authors.affiliation: Gastroenterology Unit, Antoine Béclère Hospital, Clamart, France.
authors.forename: Lysiane
authors.initials: L
authors.lastname: Marthey
authors.affiliation: Gastroenterology and Digestive Unit, Georges Pompidou European Hospital, Paris, France.|Paris Descartes University-Sorbonne Paris Cité, Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Taieb
authors.affiliation: Department of Medical Oncology, Curie Institute Hospital, Paris, France.
authors.forename: Wulfran
authors.initials: W
authors.lastname: Cacheux
authors.affiliation: Department of Medical Oncology, René Huguenin Hospital, Curie Institute, Saint-Cloud, France.|Faculty of Health Sciences, Versailles Saint-Quentin-en-Yvelines University, Montigny-Le-Bretonneux, France.
authors.forename: Astrid
authors.initials: A
authors.lastname: Lièvre
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011379:Prognosis; D016016:Proportional Hazards Models; D016879:Salvage Therapy / Q000379:methods*; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine
keywords: advanced biliary tract cancer; fluoropyrimidine; overall survival; prognostic factors; progression-free survival; second-line chemotherapy