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Radium-223 chloride: a potential new treatment for castration-resistant prostate cancer patients with metastatic bone disease

Authors Harrison MR, Wong TZ, Armstrong AJ, George DJ

Received 30 May 2012

Accepted for publication 6 August 2012

Published 8 January 2013 Volume 2013:5 Pages 1—14

DOI https://doi.org/10.2147/CMAR.S25537

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Michael R Harrison, Terence Z Wong, Andrew J Armstrong, Daniel J George

Duke Cancer Institute, Durham, NC, USA

Background: Radium-223 chloride (223Ra; 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), 223Ra delivers a high quantity of energy per track length with short tissue penetration.
Objective: This review describes the mechanism, radiobiology, and preclinical development of 223Ra 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.
Conclusion: 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, 223Ra 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, 223Ra 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.

Keywords: Alpharadin, 223Ra, radium-223, radionuclide therapy, metastatic castrate-resistant prostate cancer, bone metastases

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