Alpha Emitter Radium-223 and Survival in Metastatic Prostate Cancer
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- 18 July 2013
- journal article
- research article
- Published by Massachusetts Medical Society in The New England Journal of Medicine
- Vol. 369 (3), 213-223
- https://doi.org/10.1056/nejmoa1213755
Abstract
Radium-223 dichloride (radium-223), an alpha emitter, selectively targets bone metastases with alpha particles. We assessed the efficacy and safety of radium-223 as compared with placebo, in addition to the best standard of care, in men with castration-resistant prostate cancer and bone metastases. In our phase 3, randomized, double-blind, placebo-controlled study, we randomly assigned 921 patients who had received, were not eligible to receive, or declined docetaxel, in a 2:1 ratio, to receive six injections of radium-223 (at a dose of 50 kBq per kilogram of body weight intravenously) or matching placebo; one injection was administered every 4 weeks. In addition, all patients received the best standard of care. The primary end point was overall survival. The main secondary efficacy end points included time to the first symptomatic skeletal event and various biochemical end points. A prespecified interim analysis, conducted when 314 deaths had occurred, assessed the effect of radium-223 versus placebo on survival. An updated analysis, when 528 deaths had occurred, was performed before crossover from placebo to radium-223. At the interim analysis, which involved 809 patients, radium-223, as compared with placebo, significantly improved overall survival (median, 14.0 months vs. 11.2 months; hazard ratio, 0.70; 95% confidence interval [CI], 0.55 to 0.88; two-sided P=0.002). The updated analysis involving 921 patients confirmed the radium-223 survival benefit (median, 14.9 months vs. 11.3 months; hazard ratio, 0.70; 95% CI, 0.58 to 0.83; P<0.001). Assessments of all main secondary efficacy end points also showed a benefit of radium-233 as compared with placebo. Radium-223 was associated with low myelosuppression rates and fewer adverse events. In this study, which was terminated for efficacy at the prespecified interim analysis, radium-223 improved overall survival. (Funded by Algeta and Bayer HealthCare Pharmaceuticals; ALSYMPCA ClinicalTrials.gov number, NCT00699751.)Keywords
This publication has 26 references indexed in Scilit:
- Potential synergistic implications for stromal-targeted radiopharmaceuticals in bone-metastatic prostate cancerAsian Journal of Andrology, 2011
- Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind studyThe Lancet, 2011
- Implications of Bone Metastases and the Benefits of Bone-Targeted TherapySeminars in Oncology, 2010
- Randomized Phase II Trial of Denosumab in Patients With Bone Metastases From Prostate Cancer, Breast Cancer, or Other Neoplasms After Intravenous BisphosphonatesJournal of Clinical Oncology, 2009
- Radioisotopes for the palliation of metastatic bone cancer: a systematic reviewThe Lancet Oncology, 2005
- Docetaxel plus Prednisone or Mitoxantrone plus Prednisone for Advanced Prostate CancerThe New England Journal of Medicine, 2004
- Mechanisms of Bone MetastasisThe New England Journal of Medicine, 2004
- Systemic radiopharmaceutical therapy of painful osteoblastic metastasesSeminars in Radiation Oncology, 2000
- Mechanisms, hypotheses and questions regarding prostate cancer micrometastases to bone.Cancer and Metastasis Reviews, 1998
- Bisphosphonates in prostate carcinomaCancer, 1997