The aim of this article was to describe some of the most interesting developments concerning new therapies for advanced prostate cancer.
During the last years new experimental therapeutic agents for the treatment of advanced prostate cancer have been developed. These are based on the recent discoveries on prostate cell function, resistance to chemotherapy, tumor immunology (relation between cancer cells and the immune system) and the role of androgens (male hormones).
The hormonal treatment was the most important therapy for a long time but despite the blockade of androgens (androgen suppression therapy), some cancers progress and the rate of 5-year survival (percentage of patients still alive 5 years after diagnosis) is approximately 25%. Understanding the action mechanisms of androgens seems to be the key for new treatments. One strategy has been to block androgen production using Ketoconazole (Nizoral – inhibits androgen production and lowers testosterone levels). When used in the castrate-resistant prostate cancer (a cancer that does not respond to hormonal therapy), PSA responses were observed in 20 – 60% of patients and lasted for 3 – 7 months; however, at the dose given, the high toxicity of this product can limit its clinical use.
In prostate cancer, high levels of an enzyme (protein that speeds up chemical reactions in the body) called CYP17 were observed and this led to the synthesis of Abiraterone (Zytiga). This treatment had >50% reduction in PSA level, in more than 50% of the patients with or without prior chemotherapy treatment.
Among the most efficient chemotherapy drugs was Carbazitaxel (Jevtana), approved in the US but not in UK yet. This treatment showed an increase of approximately 3 months in survival rates.
Immunotherapy (modification of the immune response) is not yet well documented as being of great utility in this medical condition. However, one vaccine is approved for the use of metastatic hormone refractory prostate cancer (HRPC – prostate cancer that does not respond to hormonal therapy and spread to distant sites) – Sipuleucel-T. This showed a survival benefit of about 4.1 months but no shrinkage of the tumor.
Since prostate cancer spreads fast to the bone (bone metastasis), strategies were considered to target the involved mechanisms. Denosumab (Xgeva – a substance that inhibits bone destruction) showed a significantly decreased rate of bone fractures but did not affect survival.
The last 5 years brought a great change in the understanding of the molecular mechanisms underlying HRPC. Due to the prospective addition of more available drugs for HRPC, treatment will probably become much more complex. In addition, patients will have to be carefully selected according to their general health status, cancer-related features and prior treatment attempts.
