Radium-223 is safe and effective when combined with other therapies

This study examined the safety and effectiveness of radium-223, alone or in combination with other therapies, in treating metastatic castration-resistant prostate cancer (mCRPC). Researchers concluded that radium-223 was well tolerated and can be safely combined with additional therapies. Combined therapies were associated with improved overall survival. 

Metastatic castration-resistant prostate cancer (mCRPC) is prostate cancer than continues to spread despite standard hormone therapy. The most common site of cancer spread (metastases) is on the bone. Bone tumors can cause significant pain and other complications such as fractures or nerve compressions.

Chemotherapy is usually prescribed for mCRPC. However, many men do not tolerate chemotherapy and require alternative treatment. Radium-223 is a radiation drug developed for advanced prostate cancer that specifically targets bone metastases. Early studies have demonstrated a survival advantage and reduced cancer pain with radium-223. More studies are needed to examine radium-223 for mCRPC and whether it can be safely combined with other alternative therapies, such as secondary hormone therapies (including abiraterone [Zytiga] and enzalutamide [Xtandi]).

This study included 696 men with mCRPC. All men received treatment with radium-223 (every 4 weeks for up to 6 injections). 60% of men had previously received chemotherapy. During treatment with radium-223, 14% received additional radiation therapy, 20% received additional abiraterone, and 5% received additional enzalutamide. Additional bone-targeting drugs, such as bisphosphonates or denosumab, were administered in 19 to 20% of men receiving radium-223. Patients were followed for an average of 7.5 months.

210 deaths were reported during the study period. Average overall survival (time from treatment until death from any cause) was 16 months. Overall survival was significantly longer among men receiving abiraterone or enzalutamide in addition to radium-223. This was particularly pronounced for men who had never received abiraterone or enzalutamide before the study. Overall survival was also increased if denosumab was administered during radium-223 treatment. Additional treatment with bisphosphonates had no effect on overall survival. No difference in survival was found for men previously treated with chemotherapy or not.

Men with lower alkaline phosphatase levels (enzyme in the blood indicating bone tumor growth) before the study showed a significant benefit in overall survival. Overall survival was also longer among men with higher hemoglobin levels (red protein in the blood transporting oxygen), better functioning of daily living activities, and less cancer pain.

75% of men experienced at least one treatment-related side effect. 35% of side effects were considered serious. The most common serious side effects included low red blood cell count, low platelet count, and low white blood cell count. 21% of men discontinued radium-223 treatment due to side effects. There were no significant differences in the rate of side effects for men receiving additional therapies. 

Researchers concluded that radium-223 was well tolerated and can be safely combined with additional therapies. Adding abiraterone, enzalutamide, or denosumab to radium-223 treatment was associated with longer overall survival.