FDA Approval for Radium 223 Dichloride

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Brand name(s): Xofigo

  • Approved for castration-resistant prostate cancer with bone metastases

Full prescribing information is available, including clinical trial information, safety, dosing, drug-drug interactions, and contraindications.

On May 15, 2013, the Food and Drug Administration (FDA) approved radium 223 dichloride (Xofigo Injection, made by Bayer HealthCare Pharmaceuticals Inc.) for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases, and no known visceral metastatic disease. Radium 223 dichloride, also known as Radium Ra 223 dichloride, is an alpha-particle emitting radiotherapeutic drug that mimics calcium and forms complexes with hydroxyapatite at areas of increased bone turnover, such as bone metastases.

The approval was based on a double-blind, randomized placebo-controlled trial in patients with metastatic castration-resistant prostate cancer who had symptomatic bone metastases and no known visceral metastatic disease. The patients were randomly assigned (2:1) to receive radium 223 dichloride, 50 kBq/kg (1.35 microcurie/kg), intravenously, every 4 weeks for 6 cycles plus best standard of care (N=541) or a matching placebo plus best standard of care (N=268).  Best standard of care included local radiotherapy, corticosteroids, antiandrogens, estrogens, estramustine, or ketoconazole.  All patients were to continue androgen deprivation therapy. The median patient age was 71 years, 94 percent were Caucasian, 86 percent had an ECOG performance status of 0-1, and 58 percent had received prior docetaxel chemotherapy. Fifty-four percent of patients used opiate pain medications and 44 percent used non-opiate medications.  Overall survival (OS) was the primary endpoint.

At the pre-specified interim analysis, a statistically significant improvement in OS was demonstrated (hazard ratio: 0.70; 95 percent confidence interval: 0.55, 0.88; p = 0.00185). The median OS was 14.0 months for patients treated with radium 223 dichloride and 11.2 months for patients treated with placebo. The improvement in OS was supported by a delay in time-to-first symptomatic skeletal event for patients treated with radium 223 dichloride.

The most common (at least 10 percent) adverse reactions in patients receiving radium 223 dichloride were nausea, diarrhea, vomiting, and peripheral edema. The most common (at least 10 percent) hematologic laboratory abnormalities were anemia, lymphocytopenia, leukopenia, thrombocytopenia, and neutropenia. Two percent of patients treated with radium 223 dichloride experienced bone marrow failure or ongoing pancytopenia. No patients treated with placebo experienced bone marrow failure or pancytopenia.

The recommended dose and schedule for  radium 223 dichloride are 50 kBq/kg (1.35 microcuries/kg) administered by slow intravenous injection over 1 minute every 4 weeks for 6 doses.

This summary was provided by Richard Pazdur, M.D., director of the FDA's Division of Oncology Drug Products, or Patricia Keegan, M.D., director of the FDA's Division of Clinical Trials Design and Analysis.

The FDA is the division of the U.S. Department of Health and Human Services charged with ensuring the safety and effectiveness of new drugs and other products. (See "Learn How Drugs and Devices Get Approved.") The FDA's mission is to promote and protect the public health by helping safe and effective products to reach the market in a timely way, and monitoring products for continued safety after they are in use.

For further information related to oncology drug approvals, regulatory information and other oncology resources, please refer to the FDA's Oncology Tools Web site.

  • Updated: July 3, 2013