A new type of treatment that alternately floods and starves the body of testosterone has shown good early results in men with advanced prostate cancer, according to new findings revealed today.

1 Dec 2016

Drastically altering the levels of testosterone could cause cancer cells to die even after they become hormone-resistant, according to new research unveiled today. The results from the early-stage study of 47 men were presented at a symposium in Munich, Germany.

"Our goal is to shock the cancer cells by exposing them rapidly to very high followed by very low levels of testosterone in the blood," explained Prof Denmeade from the research team. These alternating extremes in testosterone levels are why the researchers call the therapy "bipolar androgen therapy".

Intriguing approach with unexpected results

Traditionally, treatments for prostate cancer have involved lowering the levels of the male hormone (or androgen) testosterone by what is known as androgen deprivation therapy.

Dr Matthew Hobbs, Deputy Director of Research at Prostate Cancer UK, said: "Androgen deprivation therapy is an effective treatment for thousands of men with advanced prostate cancer. However, at some point the cancer evolves and those drugs stop working.

"This research is intriguing because it offers a hint that – somewhat unexpectedly – for some men whose cancers have reached that 'hormone resistant' stage, it may be possible to kill or stop growth of the cancer cells by actually overloading them with testosterone."

Cancer cells can develop resistance to hormone therapy and drugs like abiraterone and enzalutamide. But this can leave them vulnerable in other ways. These results indicate that they could become sensitive to high amounts of testosterone after getting used to being deprived. By switching back and forth between floods and droughts, the cancer is constantly kept on its toes and could stop it from becoming resistant.

Work in progress still and unsuitable for all

The research is still a work in progress and the final results have not been published yet. The researchers have completed one arm of their study involving 30 men, whose cancer became resistant to enzalutamide and started to progress. After the testosterone treatment, about 40 per cent had a decrease in PSA levels and one man’s PSA even dropped to zero. A second arm of the study is ongoing with men whose disease had started to progress again after treatment with abiraterone.

Prof Denmeade said: "We caution that this is still experimental. In particular, this therapy should only be given to men who are asymptomatic. Testosterone treatment can definitely worsen pain in men with prostate cancer who have pain from their disease."

Previous trials in the 1980s that attempted to use testosterone to boost the effects of chemotherapy resulted in severe side effects in some men. Although this new research is different, men enrolled on further trials in this area will need to be monitored closely.

Many exciting new lines of attack against prostate cancer are emerging of which this is one

- Dr Matthew Hobbs, Deputy Director of Research, Prostate Cancer UK

Another trial in the US is testing this approach compared to enzalutamide in men with hormone-resistant prostate cancer whose disease had progressed after being treated with abiraterone.

"Many exciting new lines of attack against prostate cancer are emerging of which this is one," said Dr Matthew Hobbs concluded. "However, this is early stage research and further studies are needed in order to understand exactly how intriguing developments like this work and to test the findings more robustly in large clinical trials.

"Prostate Cancer UK is committed to funding the research that will be essential if we are to capitalise on early results like these to dramatically reduce the number of men dying from prostate cancer."

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