title: Clinical Outcomes of Castration-resistant Prostate Cancer Treatments Administered as Third or Fourth Line Following Failure of Docetaxel and Other Second-line Treatment: Results of an Italian Multicentre Study.
abstract: BACKGROUND
  The availability of new agents (NAs) active in patients with metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel treatment (abiraterone acetate, cabazitaxel, and enzalutamide) has led to the possibility of using them sequentially to obtain a cumulative survival benefit.
  
  
  OBJECTIVE
  To provide clinical outcome data relating to a large cohort of mCRPC patients who received a third-line NA after the failure of docetaxel and another NA.
  
  
  METHODS
  We retrospectively reviewed the clinical records of patients who had received at least two successive NAs after the failure of docetaxel.
  
  
  METHODS
  The independent prognostic value of a series of pretreatment covariates on the primary outcome measure of overall survival was assessed using Cox regression analysis.
  
  
  CONCLUSIONS
  We assessed 260 patients who received one third-line NA between January 2012 and December 2013, including 38 who received a further NA as fourth-line therapy. The median progression-free and overall survival from the start of third-line therapy was, respectively, 4 mo and 11 mo, with no significant differences between the NAs. Performance status, and haemoglobin and alkaline phosphatase levels were the only independent prognostic factors. The limitations of the study are mainly due its retrospective nature and the small number of patients treated with some of the sequences.
  
  
  CONCLUSIONS
  We were unable to demonstrate a difference in the clinical outcomes of third-line NAs regardless of previous NA therapy.
  
  
  RESULTS
  It is debated which sequence of treatments to adopt after docetaxel. Our data do not support the superiority of any of the three new agents in third-line treatment, regardless of the previously administered new agent.
authors.affiliation: Medical Oncology Department, Santa Chiara Hospital, Trento, Italy. Electronic address: orazio.caffo@apss.tn.it.
authors.forename: Orazio
authors.initials: O
authors.lastname: Caffo
authors.affiliation: Medical Oncology Department, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Ugo
authors.initials: U
authors.lastname: De Giorgi
authors.affiliation: Medical Oncology Department, National Cancer Institute, Aviano, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Fratino
authors.affiliation: Department of Radiological, Oncological and Anatomopathological Sciences, La Sapienza, University of Rome, Rome, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Alesini
authors.affiliation: Medical Oncology Unit 1, Istituto Oncologico Veneto IOV - IRCCS, Padua, Italy.
authors.forename: Vittorina
authors.initials: V
authors.lastname: Zagonel
authors.affiliation: Division of Medical Oncology, Department of Uro-Gynaecological Oncology, Istituto Nazionale Tumori "Fondazione G. Pascale" - IRCCS, Naples, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Facchini
authors.affiliation: Medical Oncology Department, General Hospital, Parma, Italy.
authors.forename: Donatello
authors.initials: D
authors.lastname: Gasparro
authors.affiliation: Medical Oncology I - Candiolo Cancer Institute - FPO, IRCCS, Candiolo, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Ortega
authors.affiliation: Medical Oncology Department, University of Torino, San Luigi Hospital, Orbassano, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Tucci
authors.affiliation: Medical Oncology Department, Villa Sofia Cervello Hospital, Palermo, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Verderame
authors.affiliation: Medical Oncology Department, General Hospital, Lugo di Romagna, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Campadelli
authors.affiliation: Medical Oncology Department, Santa Maria degli Angeli Hospital, Pordenone, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Lo Re
authors.affiliation: Medical Oncology Department, Fondazione Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Procopio
authors.affiliation: Medical Oncology Division, Azienda Ospedaliero Universitaria, Policlinico di Modena, Modena, Italy.
authors.forename: Roberto
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authors.lastname: Sabbatini
authors.affiliation: Medical Oncology Department, General Hospital, Cremona, Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Donini
authors.affiliation: Medical Oncology Department, Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Morelli
authors.affiliation: Medical Oncology Department, General Hospital, Mirano, Italy.
authors.forename: Donata
authors.initials: D
authors.lastname: Sartori
authors.affiliation: Department of Medical Oncology and Haematology, Humanitas Clinical and Research Center, Rozzano, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Zucali
authors.affiliation: Medical Oncology Department, General Hospital, Faenza, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Carrozza
authors.affiliation: Medical Oncology Department, San Vincenzo Hospital, Taormina, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: D'Angelo
authors.affiliation: Division of Medical Oncology, San Giacomo Hospital, Castelfranco Veneto, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Vicario
authors.affiliation: Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Massari
authors.affiliation: Medical Oncology Department, University Campus bio-Medico, Rome, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Santini
authors.affiliation: Medical Oncology Department, General Hospital, Verona, Italy.
authors.forename: Teodoro
authors.initials: T
authors.lastname: Sava
authors.affiliation: Medical Oncology Department, Papa Giovanni XXIII Hospital, Bergamo, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Messina
authors.affiliation: Medical Oncology Department, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Fornarini
authors.affiliation: Medical Oncology Department, General Hospital, Imola, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: La Torre
authors.affiliation: Medical Oncology Department, Niguarda Cancer Centre, Ospedale Niguarda Ca' Granda, Milan, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Ricotta
authors.affiliation: Medical Oncology Department, Referral Cancer Centre of Basilicata-IRCCS, Rionero in Vulture, Italy.
authors.forename: Michele
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authors.lastname: Aieta
authors.affiliation: Medical Oncology Department, General Hospital, Carpi, Italy.
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authors.initials: C
authors.lastname: Mucciarini
authors.affiliation: Medical Oncology Unit 1, Istituto Oncologico Veneto IOV - IRCCS, Padua, Italy.
authors.forename: Fable
authors.initials: F
authors.lastname: Zustovich
authors.affiliation: Medical Oncology Department, Santa Maria della Misericordia University Hospital, Udine, Italy.
authors.forename: Sveva
authors.initials: S
authors.lastname: Macrini
authors.affiliation: Medical Oncology Department, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Salvatore Luca
authors.initials: SL
authors.lastname: Burgio
authors.affiliation: Medical Oncology Department, National Cancer Institute, Aviano, Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: Santarossa
authors.affiliation: Division of Medical Oncology, Department of Uro-Gynaecological Oncology, Istituto Nazionale Tumori "Fondazione G. Pascale" - IRCCS, Naples, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: D'Aniello
authors.affiliation: Medical Oncology Unit 1, Istituto Oncologico Veneto IOV - IRCCS, Padua, Italy.
authors.forename: Umberto
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authors.lastname: Basso
authors.affiliation: Medical Oncology Department, General Hospital, Parma, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Tarasconi
authors.affiliation: Department of Radiological, Oncological and Anatomopathological Sciences, La Sapienza, University of Rome, Rome, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Cortesi
authors.affiliation: Medical Oncology Department, University of Torino, San Luigi Hospital, Orbassano, Italy.
authors.forename: Consuelo
authors.initials: C
authors.lastname: Buttigliero
authors.affiliation: Medical Oncology I - Candiolo Cancer Institute - FPO, IRCCS, Candiolo, Italy.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Ruatta
authors.affiliation: Medical Oncology Department, Santa Chiara Hospital, Trento, Italy.
authors.forename: Antonello
authors.initials: A
authors.lastname: Veccia
authors.affiliation: Medical Oncology Department, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Vincenza
authors.initials: V
authors.lastname: Conteduca
authors.affiliation: Medical Oncology Department, Santa Chiara Hospital, Trento, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Maines
authors.affiliation: Medical Oncology Department, Santa Chiara Hospital, Trento, Italy.
authors.forename: Enzo
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authors.lastname: Galligioni
mesh_terms: D000069501:Abiraterone Acetate / Q000627:therapeutic use*; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D015331:Cohort Studies; D018572:Disease-Free Survival; D000077143:Docetaxel; D006801:Humans; D007558:Italy; D008297:Male; D015999:Multivariate Analysis; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016016:Proportional Hazards Models; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy*; D012189:Retrospective Studies; D043823:Taxoids / Q000627:therapeutic use*; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D009570:Nitriles; D043823:Taxoids; D000077143:Docetaxel; D010669:Phenylthiohydantoin; C552428:cabazitaxel; C540278:enzalutamide; D000069501:Abiraterone Acetate
keywords: Abiraterone acetate; Cabazitaxel; Castration-resistant prostate cancer; Enzalutamide; Fourth line; Prognostic factors; Third line