Metastatic, hormone-resistant (castrate-resistant) prostate cancer metastasizes primarily to the bone. Extensive bone metastasis can be very painful and cause weakness that impairs quality of life. As such, treatment that improves both quality of life and and survival is needed. Prostate cancer mortality is directly related to metastatic bone disease or its complications.
On May 15, 2013, the U. S. Food and Drug Administration approved radium 223 otherwise known as Xofigo for the treatment of patients with symptomatic bone metastases, without metastases to other visceral (soft tissue) sites. Xofigo is the sixth new agent the FDA has approved for advanced cancer in the last five years. It is a radio-therapeutic that mimics calcium, allowing it to form complexes with hydroxyapatite in areas of increased bone turnover; it homes in on and delivers a potent form of alpha-particle radiation right at the location of bone metastases.
The FDA approved Xofigo after a double-blind, randomized trial (ALSYMPCA) in patients with symptomatic bone metastases showed prolonged survival compared to men treated with a placebo. In the study, men were randomized either to Xofigo plus best standard of care, given every 4 weeks for a total of 6 cycles or to an indistinguishable placebo plus best standard of care. All patients were told to continue androgen deprivation therapy. The average age of the participants was 71. Fifty-eight percent of the men in the study had received prior chemotherapy with docetaxel (Taxotere). At the time the study began, about half of the men were taking a narcotic pain medication. Treatment administration consisted of slow (1 minute) intravenous injection once every 4 weeks. Treatment stopped after six cycles had been administered.
The objective of the study was to determine the overall survival benefits of Xofigo. In this study the men who participated started with very advanced disease. Therefore, survival in both groups was short. Despite the severity of the disease, Xofigo delayed mortality to a significant degree. The study determined that median survival for men on Xofigo was 14.0 months, and 11.2 months for men treated with placebo.
Overall, Xofigo was well tolerated. Nausea and diarrhea occurred in a few patients, 2% of patients experienced bone marrow failure with ongoing low blood counts.
We are still learning about the best method for using this novel agent. For example, ongoing clinical trials will determine the benefits of continuing treatment past the currently recommended dose of 6 cycles. Studies will also need to be done to see how treatment with Xofigo can combine with other existing types of treatment such as radiation therapy, Provenge, chemotherapy, and hormone therapy. Additionally, as therapeutic options in recurrent and advanced prostate cancer are rapidly expanding, there is great need to pursue imaging approaches that will permit the monitoring of tumor responses. All together, patients and doctors battling advanced prostate cancer are getting more and more viable and effective treatment options. □