Journal of Clinical Urology

While hormonal manipulation has a pivotal role in the management of advanced prostate cancer, most patients eventually become refractory to such intervention. Until 2004, no treatment had been shown to increase survival in this group of men. Then the demonstration that docetaxel-based chemotherapy improved overall survival, compared with mitoxantrone-based chemotherapy, ushered in a new era of prostate cancer management—and a new treatment pathway. Questions persisted over optimal use of multiple lines of hormone manipulation, and the ideal time in the pathway to offer chemotherapy. The pathway now looks set to change again, as a new generation of treatments emerges from phase III clinical trials. The next challenge facing healthcare professionals in prostate cancer will be to determine the optimal way in which these new agents can be used, in sequence and/or in combination.

Just 5 years after docetaxel was recommended by the National Institute for Health and Clinical Excellence as the standard of care for metastatic castrate-resistant prostate cancer, a novel taxane—cabazitaxel—has been licensed in Europe and the USA for a similar indication. It is authorised for use in patients whose disease progresses after docetaxel, for whom it has been shown to provide a survival benefit over current palliative strategies. However, it is not the only new treatment for this population of patients. The hormonal agent abiraterone has also been licensed in the USA, and is expected to receive a European licence later this year, the sipuleucel-T vaccine has been approved in the USA, and other agents are on the near horizon. While these advances are undoubtedly welcome, much thought will need to be given to their optimal use in terms of patient selection, the timing/sequencing of treatment, and to the design of the prostate cancer treatment paradigm. It will also be important to consider the impact that new agents will have on healthcare spending and capacity.

Cabazitaxel, a novel taxane that lacks susceptibility to the drug-resistance mechanism seen with previous drugs in the same class, has demonstrated a survival benefit in metastatic castrate-resistant prostate cancer (mCRPC), plus a manageable toxicity profile. It is the first active treatment to receive a European licence for the second-line treatment of mCRPC post-docetaxel. Novel non-chemotherapeutic treatments for this indication are at various stages of development and regulatory status. These new and emerging treatments bring a potential opportunity to extend the lives of patients with mCRPC, and improve quality of life in this setting, but they also raise pertinent questions about the optimal timing and sequencing of their use. Based on my clinical experience with cabazitaxel, first as a phase III trialist, and then as a participant in an expanded-access programme, I believe that the chemotherapeutic option should be offered before non-chemotherapeutic agents, where the patient's performance status allows, so that there is an opportunity to gain the potential benefits of this treatment within the likely therapeutic window. Other second-line/third-line treatments, notably the hormonal agent abiraterone, are likely to remain useful even after a decline in the patient's performance status.

The publication of phase III data on cabazitaxel in the management of metastatic castrate-resistant prostate cancer in men previously treated with docetaxel demonstrated, for the first time, that a survival benefit can be achieved in this patient group. Optimal use of cabazitaxel will depend on appropriate patient selection and on effective management of the side effects, which have been shown to be predictable and preventable/treatable using interventions that are already familiar to chemotherapy clinics.