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

Abstract

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

Disclosure

Consultant or advisory roles: Michael R Harrison, Exelixis; Andrew J Armstrong, Sanofi, Bayer, Dendreon, Amgen, Medivation, Janssen, Active Biotech, Bristol-Myers Squibb; Daniel J George, Astellas, Aveo, Bayer, Dendreon, Exelixis, Genentech, Medivation, Novartis, Pfizer, Sanofi, Viamet. Honoraria (speaking): Andrew J Armstrong, Sanofi, Dendreon, Amgen; Daniel J George, Amgen, Dendreon, Novartis, Pfizer, Sanofi. Research funding: Michael R Harrison, Exelixis; Andrew J Armstrong, Sanofi-Aventis, Dendreon, Medivation, Janssen, Active Biotech, Imclone/Eli Lilly, Novartis, Bristol-Myers Squibb; Daniel J George, Exelixis, Genentech, GSK, Millennium, Novartis, Pfizer. Terence Z Wong reports no conflicts of interest in this work.