Effect of Radium-223 Dichloride in Breast Cancer Bone Metastasis Model 


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Radium-223 dichloride (Xofigo) is an alpha particle–emitting radiotherapeutic drug that mimics calcium and localizes to areas of high bone turnover, providing targeted therapy for skeletal metastasis. The drug was recently approved for treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases, and no known visceral metastatic disease. Suominen and colleagues assessed effects of the drug in breast cancer cell, osteoclast, and osteoblast cultures and in a mouse model of breast cancer bone metastasis. 

A single dose of radium-223 dichloride was used in three different settings mimicking the prevention or treatment of bone metastasis. In culture, radium-223 dichloride incorporated into bone matrix and inhibited proliferation of breast cancer cells and differentiation of osteoblasts and osteoclasts (all P < .001). 

In the mouse model of established bone metastasis, the drug prevented tumor-induced cachexia (0/14 vs 7/14 control mice) and decreased osteolysis by 56% and tumor growth by 43% (all P < .05). Double-strand DNA breaks were observed in cancer cells in vivo. 

In the established bone metastasis model, radium-223 dichloride extended survival as a monotherapy (29.2 days, P = .039) and in combination with zoledronic acid (31.4 days, P = .004) or doxorubicin (31.5 days, P < .001) compared with vehicle (24.9 days). Similar but more pronounced effects were observed when radium-223 dichloride was administered in a preventive or micrometastatic setting.

The investigators concluded, “Our findings strongly support the development of radium-223 dichloride for the treatment of breast cancer patients with or at high risk of developing bone metastases.” ■

Suominen MI, et al: J Natl Cancer Inst. May 16, 2013 (early release online).

 



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