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Hormone-resistant prostate cancer: the road to successful treatment
Clinical oncologist Dr Heather Payne talks about the latest developments
The 2nd European Multidisciplinary Meeting on Urological Cancers focuses on 3 key areas, one of which is prostate cancer. On Friday 27 November, sessions 1, 2 and 3 are devoted to prostate cancer and several State-of-the-Art lectures will highlight the topic. Dr Heather Payne, consultant clinical oncologist at University College London Hospitals, has been involved in the treatment of prostate cancer treatment for the last 15 years. She sees all aspects of the disease, from first diagnosis and decision making for men with early prostate cancer to Castrate Resistant Prostate Cancer (CRPC) and palliative care. She treats men with radiotherapy, brachytherapy, hormonal therapy and chemotherapy and is also actively involved in research and clinical trials. What is her opinion about CRPC, one of the biggest challenges in prostate cancer management, and the latest developments in the field?
Q: What is the current standard treatment for metastatic CRPC and how do you feel about it?
Dr Payne: “While hormone-based therapy is usually effective initially, the majority of prostate cancers become hormone resistant and eventually these patients are likely to develop metastases, after which treatment options have traditionally been limited. Bone metastases are involved in more than 80% of cases and these can cause pain and reduction of mobility and independence”.
“Chemotherapy has been used in prostate cancer for many years. The chemotherapy agent mitoxantrone in combination with prednisolone had been shown to palliate symptoms in some men with CRPC but has no impact on survival. The results of the TAX 327 trial, when published in 2004, renewed the interest in chemotherapy for men with HRPC who were treated with the agent docetaxel”, she says.
“Docetaxel based therapy is now a standard of care for CRPC and has been shown to improve survival by several months and also importantly quality of life in patients with metastatic CRPC. It has had a positive impact in prostate cancer management and has renewed interest in therapies for men with advanced CRPC. However, as a chemotherapy regimen it has associated toxicity. In addition, the age and general condition of some men with advanced prostate cancer precludes the use of systemic chemotherapy. The chemotherapy is administered as an intravenous infusion every 3 weeks for a maximum of 10 cycles of treatment. This necessitates many men travelling to a cancer centre to receive the therapy. These limitations highlight the need for additional new treatment options for patients with CRPC that combine increased survival with improved tolerability and ease of administration”, says Dr Payne.
Q: What can you tell us about recent developments in metastatic CRPC treatment?
“I think this is a very exciting time in the treatment of CRPC. Traditionally this stage of the disease had been approached with a mixture of nihilism and resignation. However in the last few years we have seen the development of many new drugs that are showing improved survival, delays in progression and improvements in quality of life for our patients”.
“There are many new drugs being assessed in clinical trials, with many different modes of action. There have been encouraging results from studies investigating newer hormonal agents such as abiraterone and MDV 3100, immunotherapy agents such as sipuleucal-T and new combinations of drugs with chemotherapy agents. In addition existing agents for treating other cancers are being trialled for this indication, such as Avastin”, according to Dr Payne.
Q: You are involved in the ENTHUSE study with a new compound, ZD4054, a specific endothelin A receptor antagonist under evaluation for the treatment of CRPC. Could you tell us about your findings?
“We are talking about an experimental drug as the phase 3 trials are still ongoing; we do not expect to see any results until later next year at the earliest. The ENTHUSE programme consists of three multicentre, international, randomised phase 3 studies which aim to assess the efficacy and safety of ZD4054 10mg daily verses placebo in three different clinical situations in patients with CRPC. The first study follows on from a promising phase 2 trial which demonstrated a 6-7 month overall survival benefit for ZD4054 when compared to placebo in men with CRPC and bone metastases. A second study is is also exploring the benefits of ZD4054 in patients with CRPC who do not have any evidence of metastatic disease and a final study is investigating the safety and efficacy of ZD4054 verses placebo in addition to docetaxel chemotherapy”.
“ZD4054 is a once-daily oral treatment. The safety profile we have seen to date suggests it has a good tolerability profile without the severe side effects chemotherapy can have”, says Heather Payne.
“ZD4054 is a specific antagonists for the endothelin A receptor with no effects on the B receptors. This is an important asset for a drug intended to treat prostate cancer, as blocking the A receptor will stop the harmful effect of endothelin in promoting tumour growth and metastases development while allowing the beneficial effects mediated via the B receptors to continue”, she concludes.
Q: How do you see the future for CRPC patients?
“Prostate cancer management in the advanced stages of the disease consists of sequential therapy. Perhaps in the future, there are a number of effective agents all showing efficacy for CRPC. This previously inconceivable concept could rapidly become a reality if these compounds continue to demonstrate the effectiveness in Phase 3 studies that have been shown in earlier trials. In this situation the tolerability, route of administration and accessibility of the drugs are going to be important factors as to the stage at which the drugs are introduced into the management plan”, according to Dr Payne.
