It is impossible to undertake a comprehensive review of all published material in the development of any set of guidelines. However it seemed useful to add an appendix to these guidelines for reference by clinicians looking for outcomes of randomised control trials in the management of locally advanced and metastatic prostate cancer. The therapies itemised were therapies for advanced or metastatic prostate cancer currently being studied in randomised controlled trials. The National Institute of Health (NIH) registrywebsite and the World Health Organization (WHO) primary and partner registries(found at www.who.int/ictp/network) were searched for randomised controlled phase III trials of treatments for advanced prostate cancer which were ongoing (trial registry updated 2000 or onwards). These registries included the National Cancer Institute’s Physician Data Query cancer clinical trials registry (www.cancer.gov) and the Australian New Zealand Clinical Trials Registry (www.anzctr.org.au). Readers are referred to these two registries for details of ongoing clinical trials for prostate cancer treatments that are recruiting in Australia.. Trials described as complete were checked for publications and trials described as terminated were checked where possible for the reasons they were terminated. Trials with mature data included in the systematic reviews or their appendices were not included. It should be noted that in most cases this summary depends on the information provided by the trial register, which is not always accurate, clear or current, and thus it is not a comprehensive review.
For men with locally advanced disease
There are numerous continuing trials examining different radiotherapy techniques, including intensity modulated radiotherapy (IMRT) and hypofractionation, dose escalation, and the addition of radiotherapy to hormone therapy and to brachytherapy. Similarly, there are numerous trials examining different regimens and types of hormone therapy as a monotherapy, as an adjuvant or neo-adjuvant to definitive therapy, and as an addition to adjuvant radiotherapy. There are also continuing trials examining docetaxel as an adjuvant to definitive therapy with or without hormone therapy, and one study currently recruiting patients for a trial of chemohormonal therapy as a neoadjuvant to prostatectomy. In contrast, only two trials were identified that examined surgery (prostatectomy and cryoablation) and it is unclear whether they include men with locally advanced disease. There are at least two trials that appear to be ongoing, which are examining the effects of zoledronic acid. A trial is planned to assess the effect of a multidisciplinary support program for patients undergoing definitive radiotherapy and a trial has been completed of the isoflavenoid genistein. For men on hormone therapy there are at least four trials testing various exercise regimens as well as a trial of green tea extract.
For men with biochemical relapse following definitive therapy
There are at least two trials examining salvage radiotherapy; numerous trials examining various hormone therapy modalities and regimens, including immediate versus delayed; and at least three trials examining chemotherapy, including docetaxel, as an adjuvant to hormone therapy. Thalidomide and rosiglitazone are also being studied. In addition, several dietary interventions are being trialled, including pomegranate juice, lycopene with vitamin E, and an intensive nutritional intervention focusing on a low-fat diet high in fibre, fruit, vegetable, green tea and vitamin E.
For men with metastatic disease
There are numerous trials studying the addition of bisphosphonates, primarily zoledronic acid, to hormone therapy. There are trials examining various hormone therapy regimens and modalities and the addition of doctaxel to hormone therapy. One trial is examining the benefits of prostate radiotherapy in addition to hormone therapy for men diagnosed with metastatic prostate cancer. For painful bone metastases, the bisphosphonate ibandronate is being studied as alternative to or in addition to radiotherapy. For spinal metastases with microfractures or compression fractures, vertebroplasty is being studied as an addition to radiotherapy. A trial of suramin in addition to hormone therapy has been completed. Suramin is a molecule that interferes with the action of a number of growth factors, including those involved in angiogenesis.
For men with castrate-resistant prostate cancer
For men with castrate-resistant prostate cancer without clinical evidence of metastases, docetaxel chemotherapy and endothelin-A receptor antagonists atrasentan and zibotentan (ZD4054) are being trialled. These patients may also be included in continuing trials for the treatment of castrate-resistant or hormone refractory prostate cancer with abiraterone, which blocks testosterone synthesis; diethylstilbestrol; the bisphosphonate risedronate; the RANK ligand antibody denosumab; the PDGFR inhibitor leflunomide; and a peptide vaccine. A trial of immediate versus delayed psychological intervention for patients with advanced cancer has been completed.
For men with castrate-resistant prostate cancer with metastases there are continuing trials of the bonetargeting radioisotope radium-223; the addition of strontium 89 to docetaxel chemotherapy; the addition of zoledronic acid to standard therapy; dexamethasone regimens; the taxoid XPR6258; doxorubicin; endothelin A antagonists atrasentan and zibotentan (ZD4054); sunitinib, a receptor kinase inhibitor, aflibercept and bevacizumab, which target VEGF, which drives angiogenesis: prinomastat, which inhibits matrix metalloproteases involved in tumour invasion, angiogenesis and metastasis; and Provenge, dendritic stem cell precursors activated by exposure to prostatic acid phosphatase. The GVax prostate vaccine trials have been terminated due to an imbalance of deaths. Finally, there is a continuing trial of Auron Misheil Therapy 2003, a combination of camomile extract calcium, vitamins, anti-histamine and insulin.
- National Institute of Health. National Institute of Health registry website. NIH 2008 Sep 1 Available from: http://www.clinicaltrials.gov/.
- World Health Organisation. World Health Organisation Primary Registry website. WHO 2008 Sep 1 Available from: http://www.who.int/network/en/index.html.