The alpha-emitter radium-223 (²²³Ra) is a bone-seeking radionuclide studied as a new treatment for patients with bone metastases from hormone-refractory prostate cancer. We aimed to study mature outcomes from a randomised, multicentre, phase II study of ²²³Ra.

Patients with hormone-refractory prostate cancer and bone pain needing external-beam radiotherapy were assigned to four intravenous injections of ²²³Ra (50 kBq/kg, 33 patients) or placebo (31 patients), given every 4 weeks. Primary endpoints were change in bone-alkaline phosphatase (ALP) concentration and time to skeletal-related events (SREs). Secondary endpoints included toxic effects, time to prostate-specific-antigen (PSA) progression, and overall survival. All tests were done at a 5% significance level, based on intention to treat.

Median relative change in bone-ALP during treatment was −65·6% (95% CI −69·5 to −57·7) and 9·3% (3·8–60·9) in the ²²³Ra group and placebo groups, respectively (p<0·0001, Wilcoxon ranked-sums test). Hazard ratio for time to first SRE, adjusted for baseline covariates, was 1·75 (0·96–3·19, p=0·065, Cox regression). Haematological toxic effects did not differ significantly between two groups. No patient discontinued ²²³Ra because of treatment toxicity. Median time to PSA progression was 26 weeks (16–39) versus 8 weeks (4–12; p=0·048) for ²²³Ra versus placebo, respectively. Median overall survival was 65·3 weeks (48·7–∞) for ²²³Ra and 46·4 weeks (32·1–77·4) for placebo (p=0·066, log rank). The hazard ratio for overall survival, adjusted for baseline covariates was 2·12 (1·13–3·98, p=0·020, Cox regression).

²²³Ra was well tolerated with minimum myelotoxicity, and had a significant effect on bone-ALP concentrations. Larger clinical trials are warranted to study ²²³Ra on the prevention of SREs and on overall survival in patients with hormone-refractory prostate cancer. Bone-targeting properties of ²²³Ra could also potentially be used for treating skeletal metastasis from other primary cancers.