Scholars@Duke publication: Radium-223 chloride: a potential new treatment for castration-resistant prostate cancer patients with metastatic bone disease.

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

Publication , Journal Article

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

Published in: Cancer Manag Res

2013

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. 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, (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.