Hormonal therapy for castration-resistant prostate cancer, are there lines of therapy?

The knowledge of hormone dependence of prostate cancer and the possibilities of interfering with it were described as early as the

1940s. In a large proportion of patients, surgical castration is replaced by medical castration by means of LHRH agonists. In order to

reduce testosterone level fluctuations during LHRH administration (mini flare-up phenomenon) and, thus, the action of non-castrate

testosterone levels during treatment on the androgen receptor, administration of LHRH antagonists is more convenient. Despite a good

and often long-term response to hormonal therapy, failure of the treatment modality occurs. The monotherapy administered initially can

be extended to maximum androgen blockade and, thus, to prolongation of the effect of hormonal therapy. Nevertheless, a malignant

tumour acquires different growth characteristics, fundamentally altering the disease prognosis and becoming castration-resistant (CRPC),

i.e. progressive with castrate testosterone levels. In the early millennium, first-line therapy for castration-resistant prostate cancer was

standardized. Administration of docetaxel with prednisone was the first treatment to have resulted in prolonged survival in patients with

CRPC. Newly registered medicinal products are compared with this regimen in terms of efficacy and the rates of adverse effects. Regimens

with immunotherapy, a novel cytotoxic drug cabazitaxel, and, in particular, the new hormonal products abiraterone and enzalutamide

are gradually emerging. A large number of agents alone or in combination with standard therapy are being investigated in clinical trials.

In the case of drugs that have already been approved, ongoing trials should address issues concerning the optimal duration of use

and the sequence of treatment. Administration of bone-metabolism modulating agents is an integral part of the treatment for mCRPC.

Keywords: castration-resistant prostate cancer (CRPC), hormonal therapy, chemotherapy, targeted therapy, novel agents