title: Radium-223 dichloride for the treatment of bone metastatic castration-resistant prostate cancer: an evaluation of its safety.
abstract: BACKGROUND
  Approximately 10 - 20% of prostate cancer cases ultimately progress to castration-resistant prostate cancer (CRPC), for which there is a poor prognosis and a therapeutic need. Radium-223 dichloride (radium-223 [Xofigo]) is a first-in-class α-emitting radiopharmaceutical shown to significantly prolong overall survival in patients with CRPC with symptomatic bone metastases and no visceral metastases. Current treatment guidelines recommended it in both pre- and post-docetaxel settings.
  
  
  METHODS
  Radium-223 mechanism of action, pharmacokinetics and key efficacy and safety data are reviewed. The evaluation of adverse events reported in the Phase III ALSYMPCA trial is summarized for the overall population and patient subpopulations (prior docetaxel, concomitant external beam radiation therapy and baseline opioid use). An evaluation of how radium-223 is being incorporated into the CRPC treatment paradigm and the implications of its safety profile for future use are provided.
  
  
  CONCLUSIONS
  The pronounced efficacy and safety profile of radium-223 positions it as a valuable new therapeutic tool in the CRPC armamentarium. Its novel mechanism of action underlies low rates of hematologic adverse events. Radium-223 treatment will become common in the majority of pre-docetaxel symptomatic CRPC cases, as it has proved to be highly efficient with few safety concerns earlier in the course of disease.
authors.affiliation: Karolinska University Hospital , Stockholm , Sweden Sten.nilsson@ki.se.
authors.forename: Sten
authors.initials: S
authors.lastname: Nilsson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000097:blood; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols; D001682:Biological Availability; D001859:Bone Neoplasms / Q000097:blood / Q000188:drug therapy / Q000556:secondary; D016723:Bone Remodeling / Q000187:drug effects*; D024042:Collagen Type I / Q000097:blood; D000077143:Docetaxel; D016903:Drug Monitoring / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010455:Peptides / Q000097:blood; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy / Q000473:pathology; D011868:Radioisotopes / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D011883:Radium / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D024042:Collagen Type I; D010455:Peptides; D011868:Radioisotopes; D043823:Taxoids; C052929:collagen type I trimeric cross-linked peptide; D000077143:Docetaxel; D000469:Alkaline Phosphatase; C581106:radium Ra 223 dichloride; D011883:Radium
keywords: bone metastases; castration-resistant prostate cancer; overall survival; radium-223 dichloride; safety; α-emitter