title: Bone-targeting radiopharmaceuticals for the treatment of bone-metastatic castration-resistant prostate cancer: exploring the implications of new data.
abstract: BACKGROUND
  Clinical features of patients with castration-resistant prostate cancer (CRPC) are characterized by a high incidence of bone metastases, which are associated with impairment of quality of life, pain, skeletal-related events (SREs), and a negative impact on prognosis. Advances in the understanding of cancer cell-bone stroma interactions and molecular mechanisms have recently permitted the development of new agents.
  
  
  OBJECTIVE
  We review the merits, applications, and limitations of emerging data sets on bone-metastatic CRPC with a focus on radium-223, an α-emitting radiopharmaceutical, and its use in therapy for this disease.
  
  
  METHODS
  References for this review were identified through searches of PubMed and Medline databases, and only papers published in English were considered. Related links in the databases were reviewed, along with relevant published guidelines, recently published abstracts from major medical meetings, and transcripts from a recent round table of clinical investigators.
  
  
  RESULTS
  Prior to radium-223, available bone-targeted therapies demonstrated the ability to delay SREs and palliate bone pain in patients with metastatic CRPC but without evidence of improvement in overall survival (OS). In a randomized controlled phase III trial, radium-223 demonstrated the ability to improve OS and delay SREs in docetaxel-pretreated or docetaxel-unfit men with symptomatic bone-metastatic CRPC and was not associated with significantly more grade 3 or 4 adverse events than placebo.
  
  
  CONCLUSIONS
  Radium-223 has a targeted effect on bone metastases in CRPC and has an important role in docetaxel-pretreated or docetaxel-unfit men with symptomatic bone-metastatic CRPC.
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA; Medical Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA; Educational Concepts Group, LLC, Atlanta, Georgia, USA; Tulane Cancer Center, Departments of Medicine and Urology, Tulane Medical School, New Orleans, Louisiana, USA ryanc@medicine.ucsf.edu.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Ryan
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA; Medical Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA; Educational Concepts Group, LLC, Atlanta, Georgia, USA; Tulane Cancer Center, Departments of Medicine and Urology, Tulane Medical School, New Orleans, Louisiana, USA.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Saylor
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA; Medical Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA; Educational Concepts Group, LLC, Atlanta, Georgia, USA; Tulane Cancer Center, Departments of Medicine and Urology, Tulane Medical School, New Orleans, Louisiana, USA.
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Everly
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA; Medical Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA; Educational Concepts Group, LLC, Atlanta, Georgia, USA; Tulane Cancer Center, Departments of Medicine and Urology, Tulane Medical School, New Orleans, Louisiana, USA.
authors.forename: Oliver
authors.initials: O
authors.lastname: Sartor
mesh_terms: D000512:Alpha Particles / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D001842:Bone and Bones / Q000293:injuries; D005598:Fractures, Spontaneous / Q000188:drug therapy; D006801:Humans; D008297:Male; D059408:Pain Management / Q000379:methods; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011868:Radioisotopes / Q000627:therapeutic use; D019275:Radiopharmaceuticals / Q000627:therapeutic use*; D011883:Radium / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D011868:Radioisotopes; D019275:Radiopharmaceuticals; C581106:radium Ra 223 dichloride; D011883:Radium
keywords: Bone-metastatic castration-resistant prostate cancer; Overall survival; Pain; Radium-223; Skeletal-related events