Several newspapers reported today on a new cancer treatment. The reports said that trials of the new radioactive treatment have been so successful they have been stopped early as it would have been unethical not to offer all the patients the treatment.
The news stories are based on a phase three trial, the results of which have been presented at a conference in Stockholm. The results show that giving a drug called alpharadin to patients with advanced prostate cancer that had spread to their bones, increased the average survival (median) from 11.2 months to 14 months.
Alpharadin is made of a substance called radium 223-chloride and emits alpha particles of radiation – an extremely damaging type of radiation. Alpharadin travels to areas of high bone growth: in this case, the cancer growing in bones.
The increase in survival of the patients treated with alpharadin is significant. This was a phase 3 trial, a stage at which researchers test the safety and efficacy (how well it works) of a drug in a large population.
Importantly, these results are yet to be published in a peer-reviewed journal, and the treatment has not yet been approved by any regulatory authority so it is difficult to say when alpharadin might be available.
What are these news reports based on?
This article is based on a press release from Algeta ASA the pharmaceutical company that makes alpharadin. The trial is called the ALSYMPCA trial (Alpharadin in Symptomatic Prostate Cancer patients), the results of which were presented at the 2011 European Multidisciplinary Cancer Congress on September 24.
The treatment is being developed by Algeta ASA in collaboration with another pharmaceutical company Bayer Pharma AG, as well as researchers from the Institute of Cancer Research and Royal Marsden Hospital. The story was covered by a number of news sources, including the BBC , The Telegraph and The Mail .
What is alpharadin and what is it for?
Alpharadin is the name for radium-233 chloride, and is a radioactive substance developed for the treatment of bone tumours. It admits alpha particles of radiation, which are damaging but cannot penetrate very far into the body (only a few cells deep). This means that they cause a lot of damage but only to a small area.
Alpharadin behaves in the body in a similar manner to calcium in the bone, and therefore accumulates in areas of high bone turnover, such as in the growth of a tumour. This means it can be used to target bone tumours while only causing minimal damage to surrounding tissue.
Prostate cancer is the most common cancer in men in the UK, and is the second most common cause of cancer death in men after lung cancer. Hormonal therapies are initially effective in 80% of men with metastatic prostate cancer, but after about 18 months, the disease usually doesn’t respond to hormone treatment and progresses.
The majority of men with unresponsive prostate cancer have cancer that has spread to their bones, where it can cause bone pain, fractures and other complications. Tumours in the bone are the main cause of disability and death in patients with prostate cancer resistant to hormonal therapy.
What did the trial involve?
This international study was a double-blind, randomised placebo controlled trial at 138 centres in 19 countries. All the participants had advanced prostate cancer that was no longer sensitive to hormonal therapy (the current first line of treatment for advanced prostate cancer). The patients also couldn’t be given docetaxel (the current treatment used when hormonal therapy has failed) as they were ineligible or had been found to be insensitive to it.
In all patients, the cancer had spread to their bones and was causing pain. The patients were split into two groups, and either given alpharadin in addition to standard care (615 individuals) or placebo and standard care (307 individuals).
What did the trial find?
The main result of the trial was the improved overall survival of patients in the alpharadin group. The median overall survival was 14 months for the alpharadin group and 11.2 months for the placebo group. The researchers say that the study met its primary endpoint by significantly improving survival by 44% (hazard ratio (HR)=0.695; p=0.00185).
The overall incidence of side effects was lower with alpharadin than with placebo, and patients receiving alpharadin had less bone pain (43% versus 58% on placebo). Following analysis of the results at a planned mid-point of the trial, the trial was stopped and unblinded on ethical reasons, and all participants offered alpharadin.
When might alpharadin be available?
The manufacturers will have to submit the complete results of the trial to the regulators (the Europeans Medicine Agency) before alpharadin can be approved for marketing. The efficacy and safety of alphradin will have to be assessed in detail. Until further information is available, it is difficult to say when alpharadin might be available.
The spread of cancer to bone occurs frequently in certain late-stage cancers, such as prostate (eventually affecting 75-90% of patients), breast (affecting up to 75% of patients) and lung (affecting up to 40% of patients). This treatment, if approved, may be able to improve survival, and decrease the decline in health and quality of life. However, this study only investigated the effect in men with advanced prostate cancer that had spread to their bones.