Radium-223 for Metastatic Castrate-Resistant Prostate Cancer

Prostate cancer is a significant cause of morbidity and mortality among men worldwide. Although most patients present with localized or regional disease and experience excellent outcomes with treatment, approximately 10% to 20% of patients develop castrate-resistant prostate cancer (CRPC) within 5 years of diagnosis. Bone metastases, which can cause pain and adversely affect quality of life, are common among this population. Radium-223 has a relatively short half-life and decays via α-decay. Its daughter products, α-particles, have a short path length in tissue and exhibit high linear energy transfer. Together, these properties allow radium-223 to achieve relatively high cell kill in its target tissue while sparing the surrounding normal tissues. Administered in the clinic as radium-223 dichloride (Xofigo), radium-223 acts as a calcium mimetic in the human body, forming complexes with hydroxyapatite. In areas of high bone turnover, such as the osteoblastic bone metastases that are common in patients with CRPC, radium-223 is preferentially incorporated into the bone matrix, where it can exert an antitumor effect. In May 2013, the U.S. Food and Drug Administration approved Xofigo for use in patients with CRPC who have symptomatic bone metastases and no visceral metastases. In this topic discussion, we review the mechanism of action and clinical efficacy of radium-223 in patients with metastatic CRPC. We also discuss its administration and handling, distribution and elimination, and associated toxicities.