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Title: Radium-223 in the Treatment of Osteoblastic Metastases: A Critical Clinical Review

The element radium (Ra) was discovered by the Curies in 1898 and within a decade was in broad scientific testing for the management of several forms of cancer. The compound was known to give rise to a series of both high-energy particulate and penetrating γ-emissions. The latter found an important role in early 20th century brachytherapy applications, but the short-range α-particles seemed much less useful. Although highly cytotoxic when released within a few cell diameters of critical cell nuclei, the dense double-strand break damage was poorly repaired, and concerns regarding treatment-related toxicities and secondary malignancies halted clinical development. Moreover, the most common isotope of Ra has an exceptionally long half-life (>1600 years for {sup 226}Ra) that proved daunting when aiming for a systemic cancer therapy. Fortunately, other radium isotopes have more convenient half-lives while still producing cytotoxic α particles. Radium-223 dichloride has a half-life of 11.4 days, and this isotope was identified as an excellent candidate for radionuclide therapy of cancers metastatic to bone. The calcium-mimetic chemical properties of the radium allowed intravenous infusion with rapid uptake to sites of new bone formation. The highly efficient bone localization suggested a potential therapeutic role for osteoblastic bone metastases, and a series of phasemore » 1, 2, and 3 clinical trials was undertaken to explore this possibility. This series of clinical explorations culminated in the ALSYMPCA trial, an international, placebo-controlled, phase 3 study that accrued 921 symptomatic men with bone-metastatic, castrate-resistant prostate cancer. Results of this trial demonstrated a prolongation of overall survival, and regulatory agencies around the world have now approved this product as a treatment for advanced prostate cancer.« less
Authors:
 [1] ;  [2] ;  [3] ;  [4] ;  [5]
  1. Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)
  2. Departments of Medicine and Urology, Tulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana (United States)
  3. Department of Clinical Oncology, Institute of Cancer Research, Sutton (United Kingdom)
  4. Department of Oncology, Norwegian Radium Hospital and Institute for Clinical Medicine, University of Oslo, Oslo (Norway)
  5. Department of Radiation Oncology, University Hospitals of Cleveland and Case Western Reserve University, Cleveland, Ohio (United States)
Publication Date:
OSTI Identifier:
22458662
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 91; Journal Issue: 5; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; BRACHYTHERAPY; CALCIUM; CHEMICAL PROPERTIES; CLINICAL TRIALS; GLOBAL ASPECTS; HALF-LIFE; INFUSION; METASTASES; NEOPLASMS; PROSTATE; RADIUM; RADIUM 223; RADIUM 226; REVIEWS; SKELETON; STRAND BREAKS; TOXICITY; UPTAKE