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Targeted ?-particle therapy of bone metastases in prostate cancer.

ABSTRACT: Medical oncology is moving toward personalized and precision treatments. This evolution is spearheaded by ongoing discoveries on the fundamental machinery that controls tumor and hosts microenvironment biological behavior. ?-Particles with their high energy and short range had long been recognized as potentially useful in the treatment of cancer. More than a century after the discovery of radium by the Curies, 223Ra dichloride is now available in the expanding armamentarium of therapies for metastatic castration-resistant prostate cancer. This advance occurs in the context of several other novel therapeutics in advanced prostate cancer that include more effective androgen receptor pathway inhibition, better chemotherapy, and immunotherapy. We present a concise review on the therapeutic use of 223Ra dichloride in this clinically important setting including excerpts on the radium history, physical properties, the alpharadin in symptomatic prostate cancer clinical trial, and practical information on its use in the clinic. It is anticipated that, with the current emergence of 223Ra as a viable form of therapy, interest in and use of ?-particle therapy in the management of cancer will grow.

SUBMITTER: Jadvar H

PROVIDER: S-EPMC3874447 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Targeted α-particle therapy of bone metastases in prostate cancer.

Jadvar Hossein H Quinn David I DI

Clinical nuclear medicine 20131201 12

Medical oncology is moving toward personalized and precision treatments. This evolution is spearheaded by ongoing discoveries on the fundamental machinery that controls tumor and hosts microenvironment biological behavior. α-Particles with their high energy and short range had long been recognized as potentially useful in the treatment of cancer. More than a century after the discovery of radium by the Curies, 223Ra dichloride is now available in the expanding armamentarium of therapies for meta ...[more]

PMID: 24212441

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Project description:BackgroundHormone-refractory breast cancer metastatic to bone is a clinically challenging disease associated with high morbidity, poor prognosis, and impaired quality of life owing to pain and skeletal-related events. In a preclinical study using a mouse model of breast cancer and bone metastases, Ra-223 dichloride was incorporated into bone matrix and inhibited proliferation of breast cancer cells and differentiation of osteoblasts and osteoclasts (all P values < .001) in vitro. Ra-223 dichloride also induced double-strand DNA breaks in cancer cells in vivo.MethodsThe US Food and Drug Administration recently approved radium-223 (Ra-223) dichloride (Ra-223; Xofigo injection) alpha-particle therapy for the treatment of symptomatic bone metastases in patients with castration-resistant prostate cancer. On the basis of a strong preclinical rationale, we used Ra-223 dichloride to treat bone metastases in a patient with breast cancer.ResultsA 44-year-old white woman with metastatic breast cancer who was estrogen receptor-positive, BRCA1-negative, BRCA2-negative, PIK3CA mutation (p.His1047Arg) positive presented with diffuse bony metastases and bone pain. She had hormone refractory and chemotherapy refractory breast cancer. After Ra-223 therapy initiation her bone pain improved, with corresponding decrease in tumor markers and mixed response in (18)F-FDG PET/CT and (18)F-NaF bone PET/CT. The patient derived clinical benefit from therapy.ConclusionWe have shown that Ra-223 dichloride can be safely administered in a patient with hormone-refractory bone metastasis from breast cancer at the US FDA-approved dose for prostate cancer. Furthermore, because the treatment did not cause any drop in hematologic parameters, it has the potential to be combined with other radiosensitizing therapies, which may include chemotherapy or targeted therapies. Given that Ra-223 dichloride is already commercially available, this case report may help future patients and provide a rationale for initiating clinical research in the use of Ra-223 dichloride to treat bone metastasis from breast cancer. A randomized clinical trial is needed to provide evidence of efficacy, safety, and good outcomes.

Dataset Information

Targeted ?-particle therapy of bone metastases in prostate cancer.

Publications

Targeted α-particle therapy of bone metastases in prostate cancer.

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