The U.S. Food and Drug Administration approved radium-223 dichloride for treatment of men with metastatic castration-resistant prostate cancer that has spread to the bone.

The use of radiopharmaceuticals that home in on prostate cancer bone metastases has been fairly limited because of their toxicity profiles and suppressive effects on bone marrow. However, that may be about to change.

The U.S. Food and Drug Administration (FDA) has now approved the radiopharmaceutical radium-223 dichloride (Xofigo; Algeta and Bayer) for treatment of men with metastatic castration-resistant prostate cancer (mCRPC) that has spread to the bone.

“I see the approval of radium-223 as having the potential to strongly impact clinical practice,” notes Philip Saylor, MD, an oncologist at Massachusetts General Hospital in Boston. “The burden of advanced prostate cancer is so strongly centered on bone.”

Michael Cookson, MD, professor of urologic surgery at Vanderbilt University Medical Center in Nashville, TN, says radium-223 could potentially be used in tandem with chemotherapeutic agents like docetaxel (Taxotere; Sanofi), because it causes less bone marrow suppression than other radiopharmaceuticals.

“That is the hope, that you would be able to have a one-two punch,” says Cookson, who chaired the American Urological Association committee that established new treatment guidelines for castration-resistant prostate cancer that were released in May.

Before radium-223, strontium-89 chloride (Metastron; GE Healthcare) and samarium-153 lexidronam (Quadramet; Jazz Pharmaceuticals) had been the radiopharmaceuticals of choice for treatment of pain associated with prostate cancer bone metastases. Radium-223 and strontium-89 are calcium mimetics and samarium-153 lexidronam is a chelating agent. All three preferentially accumulate in areas of higher bone turnover and growth, such as areas of metastases.

One difference is that strontium-89 and samarium-153 emit beta particles that travel for several millimeters, potentially suppressing bone marrow function, with the result that patients can often tolerate only one or two treatments.

In contrast, radium-223 emits alpha particles, which “plays out very differently, both in theory and in practice,” explains Saylor.

Alpha particles are more energetic than beta particles, one reason that Algeta claims that radium-223 is optimized to cause double-strand DNA breaks. Alpha particles are also less penetrating, traveling less than 100 ųm, largely sparing the bone marrow. As a result, radium-223 is generally well tolerated.

Although clinical trials have shown that the benefit of strontium-89 and samarium-153 is limited to palliative pain relief, radium-223 has shown survival benefits as well.

In the ALSYMPCA randomized phase III trial that led to radium-223′s approval, patients who had not been previously treated with docetaxel (the standard first-line chemotherapeutic agent for mCRPC) received six intravenous injections of radium-223 or a placebo every four weeks. Patients who received radium-223 had a median overall survival of 14.9 months compared with 11.9 months for patients who received the placebo.

One limitation on the use of radium-223 is that the FDA approved it for metastatic prostate cancer that has spread to the bones but not to other parts of the body. “It is pretty hard to find people who have just bone metastases,” Cookson points out.

However, “radium-223 has such a favorable toxicity profile that it lends itself to a lot of treatment options,” comments Michael Harrison, MD, an oncologist at the Duke University Medical Center in Durham, NC.

For example, results from a phase I study presented on June 1 at the American Society for Clinical Oncology 2013 Annual Meeting in Chicago, IL, showed that giving radium-223 and docetaxel together was safe. A phase IIa trial is underway to compare the combination to docetaxel alone.