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

PURPOSE

To summarise data with radium-223 dichloride (RaCl), 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.

METHODS

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".

RESULTS

Forty-one publications were included (30 from the literature search and 11 from manual searches/reviews). In clinical trials in mCRPC, RaCl 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. RaCl 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.

CONCLUSIONS

RaCl has demonstrated "proof of concept" for use of TAT in cancer in clinical practice. The efficacy and safety of RaCl monotherapy have been demonstrated in mCRPC, and RaCl combination therapies are under investigation in various tumours. TAT has broad applicability across tumour types.