Alpha Emitter Radium-223 and Survival in Metastatic Prostate Cancer

SUMMARY: Radium Ra 223 dichloride (XOFIGO®) is a bone seeking alpha emitter that selectively targets areas of increased bone turnover. It induces double–stranded DNA breaks and has a very limited range path and quickly loses energy within a short distance of its source. This results in less damage to the adjacent healthy tissue. Further, unlike the dreaded Ra 226 which was first isolated by Madame Curie, XOFIGO® has a short half life of 11.4 days and rapidly decays preventing radiation exposure. In a randomized, double-blind phase III trial, 921 patients with Castrate Resistant Prostate Cancer (CRPC) who had progressed on or had not received TAXOTERE® (Docetaxel) for a variety of reasons, were randomly assigned in a 2:1 ratio to receive either XOFIGO®, with best supportive care or PLACEBO with best supportive care. Patients with visceral metastases were excluded. The primary endpoint was overall survival and secondary endpoints included time to first symptomatic skeletal event, time to increase in total alkaline phosphatase level and PSA level. There was a significant increase in the median overall survival in the XOFIGO® group compared to placebo group with a 30% reduction in the risk of death (14.9 months vs 11.3 months, HR=0.70, P<0.001). All secondary endpoints favored XOFIGO® as well. All adverse events were lower in the XOFIGO® group and myelosuppression was minimal. Unlike the bone seeking beta emitters, Strontium-89 and Samarium-153, XOFIGO®, an alpha emitter, is the only agent that has been shown to improve overall survival. Studies are underway evaluating the efficacy of chemotherapy in combination with XOFIGO®, in patients with CRPC with bone metastases. Parker C, Nilsson S, Heinrich D, et al. N Eng J Med 2013;369:213-23