Radium-223 dichloride in prostate cancer: proof of principle for the use of targeted alpha treatment in clinical practice.

Abstract

To summarise data with radium-223 dichloride (²²³RaCl₂), a mechanism-mediated targeted alpha therapy (TAT), in metastatic castration-resistant prostate cancer (mCRPC) and to chart the development of TAT in mCRPC and in other tumour types. Literature for this systematic review was identified using a PubMed search: ("targeted alpha therapy" or "targeted alpha particle therapy") or (213-bismuth or bismuth-213 or 213Bi) or (225-actinium or actinium-225 or 225Ac) or (211-astatine or astatine-211 or 211At) or (212-lead or lead-212 or 212Pb) or (227-thorium or thorium-227 or 227Th) or (223-radium or radium-223 or 223Ra or alpharadin) and (malignancy or cancer). Results were limited to English-language publications in humans, with the article type "clinical trial". Forty-one publications were included (30 from the literature search and 11 from manual searches/reviews). In clinical trials in mCRPC, ²²³RaCl₂ monotherapy is well tolerated, with significantly longer overall survival than placebo and improved quality of life. Clinical trial data have been reinforced by findings from real-world studies. ²²³RaCl₂ has also shown promise in other tumour types with bone metastases, including advanced breast cancer and advanced renal cell carcinoma (in combination with anti-vascular endothelial growth factor). Several astatine-211- and bismuth-213-labelled molecules have demonstrated anti-tumour activity and acceptable toxicity in other tumour types. ²²³RaCl₂ has demonstrated "proof of concept" for use of TAT in cancer in clinical practice. The efficacy and safety of ²²³RaCl₂ monotherapy have been demonstrated in mCRPC, and ²²³RaCl₂ combination therapies are under investigation in various tumours. TAT has broad applicability across tumour types.