By: Andrew Griffin
A man with advanced prostate cancer that didn’t seem to be treated has been “cured” by a new experimental therapy.
The new treatment involved shocking tumours to death using testosterone.
Other very ill men involved in the trial saw astonishing results, with tumours being seen to shrink and the progress of the disease stopping in its tracks.
Overall, most of the people involved in the trial seemed to undergo positive results. Scientists tested that by looking at levels of Prostate Specific Antigen (PSA), a blood marker used to monitor prostate cancer – and found that it fell in most of the 47 people involved in the study.
And one individual had so little of the market in his body – and no trace of the disease – that doctors said he appears to be cured after 22 cycles of the treatment.
The trial saw the men complete at least three cycles of what is called bipolar androgen therapy, or BAT. That sees their bodies get flooded with testosterone and then starved of it.
Until now, the male hormone had thought to help spur prostate cancer on. And so scientists have traditionally looked to treat it by cutting off the supply of testosterone.
But the new study comes off the back of lab experiments that have seen cancer cells get suppressed or even killed by blasts of the same hormone.
Professor Sam Denmeade, from Johns Hopkins University School of Medicine in Baltimore, US, who led the new study, said: “We think the results are unexpected and exciting.
“We are still in the early stages of figuring out how this works and how to incorporate it into the treatment paradigm for prostate cancer.
“Thus far we have observed dramatic PSA response in a subset of men; PSA levels declined in about 40% of men and in about 30% of men levels fell by more than 50%.
“Some men also have objective responses with a decrease in the size of measurable disease, mostly in lymph nodes. Many of the men have stable disease that has not progressed for more than 12 months.
“I think we may have cured one man whose PSA dropped to zero after three months and has remained so now for 22 cycles. His disease has all disappeared.”
Early findings from the on-going Restore study were presented at the EORTC-NCI-AACR symposium on Molecular Targets and Cancer Therapeutics in Munich, Germany.
All the patients had spreading cancer that was resistant to treatment with two of the latest hormone therapy drugs, abiraterone and enzalutamide.
The men received high dose injections of testosterone once every 28 days. At the same time, they were given a drug that stopped testosterone being produced naturally by the testicles.
“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,” said Prof Denmeade.
Six of the men tested positive for a protein called AR-V7 that may be associated with resistance to enzalutamide.
After BAT treatment, no sign of the protein was seen in the blood of all six. Two of the men had declines in PSA level of 50% or more.
The therapy appears to be well-tolerated by the patients, one man experiencing an increase in pain and another having a problem with urine retention.
Prof Denmeade said it was still not clear how the treatment worked, but it appeared to involve cell signalling and part of the process of cell division. Large doses of testosterone also seemed to cause prostate cancer cells to make breaks in their DNA.
Cancer cells stopped dividing and turned “senescent”, meaning they “become like old men who sit around and tell stories but don’t make much trouble”, said the professor.
He cautioned that the therapy was still highly experimental and only suitable for men not suffering painful symptoms.
“Testosterone treatment can definitely worsen pain in men with prostate cancer who have pain from their disease,” he said.
A multi-centre randomised US trial called Transformer is now comparing BAT with enzalutamide in men who have become resistant to abiraterone. It aims to recruit a total of 180 participants.
Prof Denmeade said: “If we find testosterone is superior then we would hope to move on to larger trials. Our problem is this is not a drug that is owned by a pharmaceutical company; it is generic testosterone. So moving forward is going to be difficult due to issues with finding funds to run a bigger trial.”
Each year around 47,000 men are diagnosed with prostate cancer in the UK and 11,000 die from the disease.
Dr Matt Hobbs, deputy director of research at the charity Prostate Cancer UK, said: “Drugs that reduce the levels of testosterone (androgen deprivation therapy) are 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.
“Many exciting new lines of attack against prostate cancer are emerging of which this is one.
“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.”
Barbara Jacoby is an award winning blogger that has contributed her writings to multiple online publications that have touched readers worldwide.