Alpha-emitter radium-223 in the management of solid tumors: current status and future directions.

Abstract

Bone metastases, which are commonly seen in patients with advanced cancers, are a major cause of skeletal events, disability, and death. Radium-223 dichloride (radium-223; Xofigo, formerly Alpharadin), a first-in-class, alpha-emitting radiopharmaceutical that selectively targets bone metastases with high-energy short-range alpha-particles, has been approved for the treatment of patients with castration-resistant prostate cancer (CRPC) with symptomatic bone metastases and no known visceral metastases. Approval is based on results of the randomized phase III trial Alpharadin in Symptomatic Prostate Cancer (ALSYMPCA), in which radium-223 prolonged overall survival and time to first symptomatic skeletal event versus placebo among patients with CRPC with symptomatic bone metastases and was generally well tolerated, with low myelosuppression rates and manageable gastrointestinal adverse events. Long-term follow-up of the ALSYMPCA safety population showed that the incidence of myelosuppression remained low among patients treated with radium-223, with no additional safety issues of acute myelogenous leukemia, myelodysplastic syndrome, aplastic anemia, or primary bone cancer within approximately 1.5 years after treatment. The radium-223 overall survival benefit and low toxicity make it an effective, well-tolerated, and novel treatment option for CRPC and symptomatic bone metastases and opens the possibility of exploring radium-223 in the treatment of bone metastases from other cancers. A phase I clinical trial of patients with breast and prostate cancer with skeletal metastases demonstrated that radium-223 was safe and well tolerated at all therapeutically relevant dosages. Moreover, a phase IIa trial of patients with advanced breast cancer and progressive bone-dominant disease demonstrated that radium-223 targeted areas of increased bone metabolism and showed biologic activity.