Prostate cancer sufferer 'cured' with male hormone testosterone
A man with advanced, treatment-resistant prostate cancer may have been "cured" by an experimental therapy that involves shocking tumours to death with testosterone.
Other seriously ill men taking part in the same trial showed responses that astounded scientists. Tumours were seen to shrink and in several patients progress of the disease was halted.
Levels of Prostate Specific Antigen (PSA), a blood marker used to monitor prostate cancer, fell in the majority of the 47 participants.
One individual whose PSA levels dropped to zero after three months and shows no remaining trace of the disease after 22 cycles of treatment appears to be cured, said the researchers
All the men taking part in the pilot trial had completed at least three cycles of "bipolar androgen therapy" (BAT) which involves alternately flooding and starving the body of the male hormone testosterone.
The treatment is revolutionary because testosterone is generally assumed to fuel prostate cancer. For decades men with advanced and spreading prostate cancer have been treated by cutting off the supply of testosterone or blocking its effects.
A common therapy is a form of chemical castration using an injected drug. Upping testosterone in a man with prostate cancer is generally considered similar to pouring petrol on a fire.
Yet laboratory experiments have hinted that blasting tumours with high levels of the hormone can suppress or even kill prostate cancer cells.
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."