title: Addition of Docetaxel to Androgen Deprivation Therapy for Patients with Hormone-sensitive Metastatic Prostate Cancer: A Systematic Review and Meta-analysis.
abstract: BACKGROUND
  Several randomized clinical trials (RCTs) have recently tested the early addition of docetaxel to androgen deprivation therapy (ADT) in hormone-sensitive metastatic prostate cancer (PCa).
  
  
  OBJECTIVE
  To perform a systematic review and meta-analysis of RCTs evaluating the combination of docetaxel and ADT in hormone-sensitive metastatic PCa. The primary end point was overall survival (OS). Secondary end point was progression-free survival. Exploratory subgroup analysis according to high-volume versus low-volume disease was performed.
  
  
  METHODS
  A systematic review of PubMed/Medline, Embase, and the proceedings of major international meetings was performed in June 2015 and updated in August 2015. Three trials were selected for inclusion.
  
  
  RESULTS
  Overall, 2951 patients were included in the three trials. Two trials enrolled only metastatic patients; in the third trial, 61% were metastatic. A total of 2262 patients (951 docetaxel and ADT; 1311 ADT alone) were metastatic. Most patients had a good performance status. In metastatic patients, the addition of docetaxel was associated with improved OS (hazard ratio [HR]: 0.73; 95% confidence interval [CI], 0.60-0.90; p=0.002), with nonsignificant heterogeneity among the three trials. Considering the whole study population (2951 patients), the addition of docetaxel was associated with a similar OS improvement (HR: 0.74; 95% CI, 0.61-0.91; p=0.003). Although with limited statistical power, no significant interaction was demonstrated between the addition of docetaxel and the high or low volume of disease (p=0.5). The addition of docetaxel was associated with improvement in progression-free survival (metastatic patients: HR: 0.63; 95% CI, 0.57-0.70; p<0.001).
  
  
  CONCLUSIONS
  This meta-analysis shows a significant OS benefit from concomitant administration of docetaxel and ADT in patients with metastatic hormone-sensitive PCa.
  
  
  RESULTS
  We synthesized the evidence available about the early administration of docetaxel in patients starting hormonal treatment for metastatic prostate cancer. Based on the results of this meta-analysis, we believe the combination of chemotherapy and hormonal treatment should be considered in fit patients.
authors.affiliation: Division of Medical Oncology, Department of Oncology, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Turin, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Tucci
authors.affiliation: Division of Medical Oncology, Department of Oncology, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Turin, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Bertaglia
authors.affiliation: Division of Medical Oncology, Department of Oncology, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Turin, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Vignani
authors.affiliation: Division of Medical Oncology, Department of Oncology, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Turin, Italy.
authors.forename: Consuelo
authors.initials: C
authors.lastname: Buttigliero
authors.affiliation: Division of Urology, Department of Oncology, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Turin, Italy.
authors.forename: Cristian
authors.initials: C
authors.lastname: Fiori
authors.affiliation: Division of Urology, Department of Oncology, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Turin, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Porpiglia
authors.affiliation: Division of Medical Oncology, Department of Oncology, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Turin, Italy.
authors.forename: Giorgio Vittorio
authors.initials: GV
authors.lastname: Scagliotti
authors.affiliation: Division of Medical Oncology, Department of Oncology, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Turin, Italy. Electronic address: massimo.dimaio@unito.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Maio
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D018572:Disease-Free Survival; D000077143:Docetaxel; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016017:Odds Ratio; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D012307:Risk Factors; D043823:Taxoids / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D043823:Taxoids; D000077143:Docetaxel
keywords: Androgen deprivation therapy; Chemotherapy; Docetaxel; Hormone-sensitive prostate cancer; Meta-analysis; Systematic review