According to an investigation reported today at the 2011 European Multidisciplinary Cancer Congress, individuals suffering with bone metastases from advanced prostate cancer have not had many options until recently. Now the first Phase II investigation of an alpha-pharmaceutical in these individuals has revealed that it can extend survival considerably.
Dr. Chris Parker, Consultant Clinical Oncologist at the Royal Marsden Hospital, London, UK, explained at the congress that the ALSYMPCA international Phase III investigation of the drug Radium-223 Chloride (Alpharadin TM) which was tested on 922 men with prostate cancer resistant to hormone therapy and who had bone metastases, came to an end early after it was revealed by an interim examination by the Independent Data Monitoring Committee (IDMC) in June 2011, that individuals were living longer receiving the best standard treatment plus radium-223 compared to patients who were receiving the same standard treatment plus placebo.
The hazard ratio was 0.695, (p = 0.00185), meaning that individuals taking radium-223 had a 30% lower rate of death in comparison to those taking placebo. Average overall survival for those taking radium-223 was discovered to be 14 months, compared with 11.2 months of those in the placebo group. Dr. Parker explained: “It would have been unethical not to offer the active treatment to those taking placebo.”
Alpha-pharmaceuticals operate by delivering tiny, highly charged and targeted doses of damaging radiation to a secondary tumor (metastasis) in the bone. Radium is almost the same to calcium as it sticks to bone, and especially to where new bone is being created, making it an extremely efficient method of delivering radiation to a target. Dr. Parker said: “It takes only a single alpha particle to kill a cell, and collateral damage is minimized because the particles have such tiny range – a few millionths of a meter (micrometers). So we can be sure that the damage is being done where it should be, to the metastasis, and very limited elsewhere.”
Because of its high tendency to metastasize to bone, they decided to investigate the drug in individuals with prostate cancer. Approximately 90% of those suffering from the disease will develop bone metastases in the advanced stage of this cancer, and in several cases metastases are not detectable elsewhere in the body. They explain that the safety profile of radium-223 was discovered to highly favourable.
Dr. Parker explained:
“Compared to chemotherapy, which affects all the tissues of the body, radium-223 is highly targeted to the bone metastases, and it has a completely different safety profile.
Side effects with radium-223 are minor. It can cause nausea, and occasional loose bowel movements, and there is a very small effect on the bone. Although it has never been rigorously compared with chemotherapy, from observing patients in the clinic it is clear that patients tolerate it much better than they do chemotherapy.”
The investigators now plan to submit their information for regulatory approval. Dr. Parker said: “I would hope that the authorities will approve radium-223 as a treatment for bone metastases in advanced prostate cancer soon. This is a common cancer – the second commonest cancer killer in men in the UK – and so it’s a big disease burden. We urgently need effective treatment for it.
I have no doubt that there will be further trials looking at a combination of radium-223 with other drugs that are currently used in prostate cancer, and that there will also be studies using radium earlier in the disease. In particular, our research was restricted to those men who were not going to receive chemotherapy for prostate cancer. It would be interesting to use radium-223 chloride before chemotherapy, since it might be even more effective in that setting.”
Dr. Parker concluded:
Written by Grace Rattue