Why Alpha Particles?

Because alpha particles have a relatively large mass they cannot penetrate most matter and can be stopped by a piece of paper. However, they are powerful enough to result in a potent cytotoxic effect.15

Beta emitters, used in older palliative therapies, produce lower-energy particles that have a longer range, which can only be halted by heavy materials, such as an aluminum plate.67

Alpha vs. beta particle comparison

ALSYMPCA Phase III Pivotal Trial

The EC approval of Xofigo is based on data from the pivotal Phase III ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial. At the interim analysis, radium-223 significantly improved overall survival (OS) [HR=0.695 (95% Cl 0.552-0.875), p=0.00185]; the median OS improvement was 2.8 months with radium-223 plus best standard of care vs. placebo plus best standard of care (median OS of 14.0 months vs. 11.2 months). In addition there was a delay in the time to first symptomatic skeletal event (SSE) for patients treated with radium-223 vs. placebo.

An updated analysis, conducted after the study was unblinded, showed a further improvement in overall survival (OS) for patients treated with radium-223 vs. placebo; the median OS improvement was 3.6 months with radium-223 plus best standard of care vs. placebo plus best standard of care (median OS of 14.9 months vs. 11.3 months); HR=0.695 (95% Cl 0.581-0.832).

In both analyses, radium-223 also showed significant improvement compared to placebo in the secondary endpoints of total time to alkaline phosphatase (ALP) progression and time to prostate-specific antigen (PSA) progression.8


  1. Xofigo® (radium Ra 223 dichloride) solution for injection Summary of Product Characteristics (SmPC). Bayer Pharma AG, 13342 Berlin, Germany. 2013.]
  2. Coleman R. Metastatic bone disease: clinical features, pathophysiology and treatment strategies. Cancer Treat Rev. 2001;27:165-176.
  3. Tannock IF, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351:1502-1512.
  4. Petrylak DP. et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advancedrefractory prostate cancer. N Engl J Med. 2004;351:1513-1520.
  5. U.S. Environment Protection Agency. Alpha Particles, http://www.epa.gov/radiation/understand/alpha.html. Accessed April 23, 2013.
  6. Petrylak DP, et al. Alpha Particles as Radiopharmaceuticals in the Treatment of Bone Metastases: Mechanism of Action of Radium-223 Chloride (Alpharadin) and Radiation. Cancer Network. Vol. 26 No. 4. http://www.cancernetwork.com/ bone-metastases/content/article/10165/20583837pageNumber=2. Accessed July 19, 2013.
  7. Nuclear Connect. Protecting Against Radiation Exposure, http://nuclearconnect.org/know-nuclear/science/protecting. Accessed July 19, 2013.
  8. Parker C, Nilsson S, Heinrich D. et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med 2013;369:213-23.