The U.S. Food and Drug Administration (FDA) has approved Xofigo, an injection of radium Ra 223 dichloride, to treat men with advanced, metastatic castration-resistant prostate cancer that has spread to bones, but not other organs.

The drug is designed for men whose cancer has spread following medical or surgical therapy to lower testosterone.

The FDA fast-tracked Xofigo, approving it three months ahead of schedule. The FDA reviewed the drug under its priority review program, which is implemented for drugs that appear to offer safe and effective therapies, with no satisfactory alternatives, or that offer significant improvements compared to existing marketed products.

"Most men with castration-resistant prostate cancer develop bone metastases, which can decrease overall survival," said Oliver Sartor, North American principal investigator for the trial and medical director of the Tulane Cancer Center. "Xofigo has demonstrated an anti-tumor effect on bone metastases and will be an important addition to the treatment of this cancer."

The active ingredient in Xofigo is the alpha particle-emitting isotope radium-223. The isotope mimics calcium and forms complexes with the bone in areas of high bone turnover, such as bone metastases. The emitted radiation breaks double-stranded DNA bonds in adjacent cells, limiting tumor growth.

Bone is the most common site to be affected by metastatic prostate cancer, and 90 percent of men with metastatic prostate cancer show evidence of bone metastases. Bone metastases is the leading cause of death and morbidity in patients with castration-resistant prostate cancer.

"Xofigo binds with minerals in the bone to deliver radiation directly to bone tumors, limiting the damage to the surrounding normal tissues," said Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research. "Xofigo is the second prostate cancer drug approved by the FDA in the past year that demonstrates an ability to extend the survival of men with metastatic prostate cancer."

The first was Xtandi, which the FDA approved in August 2012. Xtandi was approved to treat men with metastatic castration-resistant prostate cancer that has spread or recurred, even after medical or surgical therapy to minimize testosterone.

Xofigo's safety and effectiveness was measured in a clinical trial of 809 men with symptomatic castration-resistant prostate cancer that had spread to bones, but not other organs.

The results of the study showed that men taking Xofigo lived a median of 14 months, compared to 11.2 months for men taking a placebo.

Two percent of men taking Xofigo suffered bone marrow failure, resulting in two deaths, compared to no bone marrow failure among the placebo group. 54 percent of the patients who suffered bone marrow failure required blood transfusions.

The most common side effects of the drug, affecting more than 10 percent of patients, included nausea, diarrhea, vomiting, and swelling of the leg, ankle or foot. During blood testing, the most common abnormalities included low levels of red blood cells (anemia), lymphocytes (lymphocytopenia), white blood cells (leukopenia), platelets (thrombocytopenia), and infection-fighting white blood cells (neutropenia).

Xofigo is not to be used in conjunction with other chemotherapies because of the potential for additive myelosuppression. Myelosuppression is a decrease in immune cell production caused by suppression of the bone marrow.

"It is encouraging to have a new treatment for men with castration-resistant prostate cancer who are dealing with bone metastases," said Jan Manarite, senior educational facilitator for the Prostate Cancer Research Institute. "Xofigo provides another new option to treat this cancer using a different approach."

Xofigo is marketed by Bayer Pharmaceuticals, based in Wayne, New Jersey. Xtandi is marketed by Astellas Pharma U.S., based in Northbrook, Illinois, as well as Medivation, based in San Francisco, California.


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