A major UK clinical trial co-led by researchers at UCL will test whether lower doses of common hormone therapies can treat advanced prostate cancer while reducing the severe side effects many patients experience.
The ENHANCE trial, jointly funded by Cancer Research UK and Prostate Cancer UK, will recruit 1,500 men with advanced prostate cancer from hospitals across the UK to compare standard and half-dose treatment using four commonly prescribed hormone drugs. UCL is sponsoring the trial and Professor Allan Hackshaw (Director of CRUK & UCL Cancer Trials Centre, UCL Cancer Institute) is joint-lead investigator, alongside Professors Ananya Choudhury and Peter Hoskin at the University of Manchester.
Men diagnosed with advanced prostate cancer, where the disease has spread beyond the prostate, are typically treated with powerful hormone therapies that slow tumour growth. While these drugs can extend life, they can also cause debilitating side effects such as extreme fatigue, hot flushes and high blood pressure, which can make it difficult for some patients to remain on treatment.
Researchers hope the £3.2 million ENHANCE trial will show that lower doses of these drugs can be just as effective while improving patients’ quality of life. The trial has not yet been launched and is awaiting the relevant regulatory and ethics approvals.
Professor Allan Hackshaw said: "Although focus is often on cancer trials to improve survival, we also need to find more tolerable ways of treating cancer without compromising survival. Side effects of cancer therapies matter a lot to patients, especially when they are frequent.
"We believe that several modern cancer drugs can be given at a much lower dose than what they were licensed for. Not only would this improve patient’s quality of life, but healthcare costs would be lower allowing more access especially in countries that cannot afford these drugs at their current high dose. The ENHANCE study can therefore influence clinical practice worldwide.
"Furthermore, Black men are more likely to get prostate cancer, and they too suffer from the same side effects of hormone treatment. They are often under-represented in clinical trials, so the ENHANCE study is a good opportunity to show that they get the same benefits from lowering the treatment dose as other ethnic groups."
ENHANCE will compare full and half-dose treatment across four hormone therapies widely used for advanced prostate cancer: abiraterone, enzalutamide, darolutamide and apalutamide. If successful, the findings could influence prostate cancer treatment guidelines in the UK and internationally as early as 2030, improving care for thousands of men and reducing costs for the NHS.
Dr Ian Walker, Executive Director of Policy at Cancer Research UK, said: "Thanks to research, there’s been huge progress in prostate cancer treatments. Today, more than 8 in 10 men diagnosed with the disease in the UK will survive for 10 years or more. There’s more that can be done to save even more lives though, and in addition to finding more effective treatments, we need to find kinder ones too. The ENHANCE trial is looking to do just that and could mean that men affected by prostate cancer live not just longer lives but have a better quality of life."
Dr Matthew Hobbs, Director of Research at Prostate Cancer UK, said: "No man should be forced to compromise between survival and their day-to-day wellbeing. This is a crucial issue for men with prostate cancer. That’s why Prostate Cancer UK is thrilled to be working alongside Cancer Research UK, pooling our resources and expertise to deliver the impact men need by funding this bold new trial that puts men’s wellbeing at its centre."
Prostate cancer is now the most common cancer in UK men. Around 55,900* men are diagnosed each year. While survival rates have tripled since the 1970s, many men still face difficult side effects from treatment.
Retired solicitor Jonathan Edwards, 80, from Cheshire, experienced severe side effects after starting the hormone-blocking drug enzalutamide following his prostate cancer diagnosis in 2024, but when his nurse reduced the dose, his cancer remained under control and his quality of life improved dramatically.
Jonathan said: "It was such a shock when I was diagnosed. I had several health issues and after many tests was eventually told that I was suffering from prostate cancer and that it had spread beyond the prostate wall to my bones. I was referred to The Christie Hospital for treatment and was prescribed hormone blockers. The side effects made me extremely tired; I was sleeping through the day on and off and I had frequent hot flushes and generally felt weak.
"When the nurse suggested lowering the dose I was not sure what to expect. The difference soon became apparent and I felt normal again. I know that I will stay on the medication for as long as it is effective but, in the meantime, I am able to live a pretty normal life. I now exercise more and do not usually need an afternoon sleep. Happily, my PSA level started to go down until, after a few months, it was undetectable and has so far remained undetectable.
"My life has been transformed by the medication, my energy levels are higher, and I can socialise as normal. Traveling was a problem but now I can plan trips as long as I work around the 12-week cycle of injections and consultations. I am delighted that this trial has the potential to help other men going through the same thing in the future by enabling them to be treated for prostate cancer with their quality of life still largely intact."
At least 10 per cent of trial participants will be Black men. Historically under-represented in clinical trials, Black men are often treated based on data that may be less applicable to them. Although data shows Black men are more likely to develop prostate cancer, more evidence is needed to understand their risk of aggressive disease and the role of overdiagnosis.
Alongside testing lower doses, the trial will collect tissue, blood and urine samples to identify biomarkers that could help determine which men are most suitable for reduced-dose treatment, shaping more personalised care in the future.
*Based on the average annual number of new cases of prostate cancer (ICD10 C61) diagnosed in the UK in the years 2018-2019, 2021.
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