title: Second-line chemotherapy in advanced biliary cancer progressed to first-line platinum-gemcitabine combination: a multicenter survey and pooled analysis with published data.
abstract: BACKGROUND
  After progression to a standard first-line platinum and gemcitabine combination (GP), there is no established second-line therapy for patients with advanced biliary tract cancers (aBTC). Indeed, literature data suggest limited activity of most second-line agents evaluated so far.
  
  
  METHODS
  We collected a large retrospective series of aBTC patients treated with second-line chemotherapy after progression to a first-line GP regimen at different Italian institutions. We then pooled the data with those reported in previous studies, which were identified with a Medline search and the on-line abstract datasets of major international oncology meetings.
  
  
  RESULTS
  A total of 174 patients were included in the multicenter survey: response rate (RR) with second-line chemotherapy was low (3.4 %), with median PFS and OS of 3.0 months and 6.6 months, respectively. At multivariate analysis, preserved performance status, low CA19.9 levels and absence of distant metastases were favorable prognostic factors. Data from other five presented or published series were identified, for a total of 499 patients included in the pooled analysis. The results confirmed marginal activity of second-line chemotherapy (RR: 10.2 %), with limited efficacy in unselected patient populations (median PFS: 3.1 months; median OS: 6.3 months).
  
  
  CONCLUSIONS
  The current analysis highlights the limited value of second-line chemotherapy after a first-line GP combination in aBTC. While waiting for effective biologic agents in this setting, ongoing randomized trials will identify the optimal second-line chemotherapy regimen and validate prognostic factors for individual patient management.
authors.affiliation: Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126, Pisa, Italy. lorenzo.fornaro@gmail.com.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Fornaro
authors.affiliation: Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126, Pisa, Italy. caterinavivaldi@gmail.com.
authors.forename: Caterina
authors.initials: C
authors.lastname: Vivaldi
authors.affiliation: Department of Medical Oncology, San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy. cereda.stefano@hsr.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: Cereda
authors.affiliation: Unit of Medical Oncology, Institute for Cancer Research and Treatment IRCCS, Strada provinciale 142, 10060, Candiolo, Italy. francesco.leone@ircc.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Leone
authors.affiliation: Department of Oncology, University and General Hospital, P.le S. Maria della Misericordia 15, 33100, Udine, Italy. aprile.giuseppe@aoud.sanita.fvg.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Aprile
authors.affiliation: Unit of Medical Oncology 1, Istituto Oncologico Veneto, IRCCS, Via Gattamelata 64, 35138, Padova, Italy. sara.lonardi@ioveneto.it.
authors.forename: Sara
authors.initials: S
authors.lastname: Lonardi
authors.affiliation: Unit of Medical Oncology, National Cancer Institute Giovanni Paolo II, V.le Orazio Flacco 65, 70124, Bari, Italy. n.silvestris@oncologico.bari.it.
authors.forename: Nicola
authors.initials: N
authors.lastname: Silvestris
authors.affiliation: Department of Medical Oncology, University Campus Bio-Medico, via Alvaro del Portillo 21, 00128, Rome, Italy. D.Santini@unicampus.it.
authors.forename: Daniele
authors.initials: D
authors.lastname: Santini
authors.affiliation: Medical Oncology A, Regina Elena National Cancer Institute, Via E. Chianesi 53, 00144, Rome, Italy. milella@ifo.it.
authors.forename: Michele
authors.initials: M
authors.lastname: Milella
authors.affiliation: Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126, Pisa, Italy. chiaracaparello@yahoo.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Caparello
authors.affiliation: Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126, Pisa, Italy. g.musettini@gmail.com.
authors.forename: Gianna
authors.initials: G
authors.lastname: Musettini
authors.affiliation: Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126, Pisa, Italy. g.pasquini988@gmail.com.
authors.forename: Giulia
authors.initials: G
authors.lastname: Pasquini
authors.affiliation: Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126, Pisa, Italy. alfredo.falcone@med.unipi.it.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Falcone
authors.affiliation: Unit of Medical Oncology, Sant'Orsola Malpighi Hospital, University of Bologna, Via Albertoni 15, 40138, Bologna, Italy. giovanni.brandi@unibo.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Brandi
authors.affiliation: Biostatistical Unit, Regina Elena National Cancer Institute, Via E. Chianesi 53, 00144, Rome, Italy. sperduti@ifo.it.
authors.forename: Isabella
authors.initials: I
authors.lastname: Sperduti
authors.affiliation: Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126, Pisa, Italy. envasile@tin.it.
authors.forename: Enrico
authors.initials: E
authors.lastname: Vasile
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001661:Biliary Tract Neoplasms / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage*; D000077150:Oxaliplatin; D012189:Retrospective Studies; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine