title: Radium-223 chloride: a potential new treatment for castration-resistant prostate cancer patients with metastatic bone disease.
abstract: BACKGROUND
  Radium-223 chloride ((223)Ra; Alpharadin) is an alpha-emitting radioisotope that targets areas of osteoblastic metastasis and is excreted by the small intestine. When compared with beta-emitters (eg, strontium-89, samarium-153), (223)Ra delivers a high quantity of energy per track length with short tissue penetration.
  
  
  OBJECTIVE
  This review describes the mechanism, radiobiology, and preclinical development of (223)Ra and discusses the clinical data currently available regarding its safety and efficacy profile.
  
  
  METHODS
  Data from clinical trials including abstracts were collected and reviewed using the PubMed Database, as well as the American Society of Clinical Oncology abstract database.
  
  
  CONCLUSIONS
  Current bone-targeted therapies fall into two main categories: antiresorptive agents (eg, zoledronic acid, denosumab), which have been shown to delay skeletal-related events, and radiopharmaceuticals (eg, samarium-153), which may have a role in pain palliation. Historically, neither antiresorptive agents nor radiopharmaceuticals have shown definitive evidence of improved overall survival or other antitumor effects in metastatic castrate-resistant prostate cancer (mCRPC). Radiopharmaceuticals are limited by myelosuppresion, thrombocytopenia, and renal excretion. In a recently reported randomized Phase III trial in men with symptomatic bone-metastatic CRPC who had received or were ineligible for docetaxel chemotherapy, (223)Ra treatment resulted in improved overall survival and delayed skeletal-related events. Toxicity consisted of minor gastrointestinal side effects and mild neutropenia and thrombocytopenia that were rarely severe. Pending regulatory approval, (223)Ra may represent a unique and distinct option for an important subgroup of patients with mCRPC; future trials should address its use in combination or in sequence with existing and novel agents.
authors: Duke Cancer Institute, Durham, NC, USA.
authors: Michael R
authors: MR
authors: Harrison
authors: Terence Z
authors: TZ
authors: Wong
authors: Andrew J
authors: AJ
authors: Armstrong
authors: Daniel J
authors: DJ
authors: George
keywords: 223Ra; Alpharadin; bone metastases; metastatic castrate-resistant prostate cancer; radionuclide therapy; radium-223