Radium-223 in CRPC With Bone Metastases

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Radium-223 (Xofigo) is a novel alpha radiation-emitting agent with calcimimetic properties that cause it to be selectively absorbed by areas of bone with metastatic cancer, notes Steven E. Finkelstein, MD. Due to the short range and intensity of alpha particles, this agent is capable of delivering localized radiation therapy without disturbing the bone marrow itself, unlike previous radiotherapies.

In May 2013, the FDA approved radium-223 as a treatment for patients with symptomatic bone-metastatic castration-resistant prostate cancer (mCRPC). This approval was based on the phase III ALSYMPCA trial that randomized patients with mCRPC to receive best supportive care plus radium-223 or placebo.

In the trial, overall survival (OS) with radium-223 was 14.9 months compared with 11.3 months with placebo. Approximately 40% of patients treated with radium-223 had not yet received chemotherapy, placing these patients in the care of a urologist, E. David Crawford, MD, suggests. Additionally, the therapy was not explored solely in patients experiencing severe pain.

Overall, treatment with radium-223 demonstrated a low incidence of myelosuppression and there was not an association with secondary malignancies. These secondary endpoints are important, since previous generations of radiopharmaceuticals were shown to be very toxic, states Crawford.

An authorized user, such as a radiation oncologist or nuclear medicine physicians, administers treatment with radium-223 in 6 intravenous injections once every 4 weeks. The exact specialist that administers radium-223 could vary from practice-to-practice, notes Vahan Kassabian, MD. However, no matter where it is administered, Kassabian believes the urologist should remain the lead physician. As an intravenous medication, the copayments for patients are lower, notes Finkelstein. This is important, David Albala, MD, believes, since reimbursement issues are a main concern in the community setting, as a newly approved drug.

Before treatment can be administered, there needs to be some type of indication of bone activity, such as elevation of alkaline phosphatase, notes David I. Quinn, MD. However, bone metastases can be present long before pain or alkaline phosphatase levels are elevated, Quinn adds.

The detection of bone metastases in asymptomatic patients using enhanced imaging could advance this therapy into earlier lines of therapy, believes Finkelstein. Additionally, this could allow radium-223 to be explored in combination with other agents approved for asymptomatic CRPC, such as sipuleucel-T.

Combination strategies have set the paradigm in other types of cancer where a cure has been achieved, notes Crawford. However, the main concern with combinations in CRPC is the substantial cost associated with care. If successful, this approach would not require long-term treatment with these drugs, minimizing costs, states Crawford. Instead, they could be administered over 3 to 4 months, until a cure is achieved, Crawford speculates.

It is possible that for some patients prostate cancer has been cured, since they appear to be dying with the disease but not from it, suggests Stephen J. Freedland, MD. For these patients, the emphasis should be placed on ensuring the patient is exercising, eating right, and other holistic approaches, Freedland believes.