Radium-223 in the treatment of osteoblastic metastases: A critical clinical review Journal Article


Authors: Humm, J. L.; Sartor, O.; Parker, C.; Bruland, O. S.; MacKlis, R.
Article Title: Radium-223 in the treatment of osteoblastic metastases: A critical clinical review
Abstract: 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 226Ra) 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 phase 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. © 2015 Elsevier Inc.
Keywords: overall survival; bone metastasis; isotopes; pathology; oncology; urology; bone; prostate cancers; diseases; alpha particles; regulatory agencies; double strand breaks; clinical development; radium; radionuclide therapy; radium isotopes
Journal Title: International Journal of Radiation Oncology, Biology, Physics
Volume: 91
Issue: 5
ISSN: 0360-3016
Publisher: Elsevier Inc.  
Date Published: 2015-04-01
Start Page: 898
End Page: 906
Language: English
DOI: 10.1016/j.ijrobp.2014.12.061
PROVIDER: scopus
PUBMED: 25832684
DOI/URL:
Notes: Export Date: 2 April 2015 -- Source: Scopus
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  1. John Laurence Humm
    374 Humm