Degarelix : a new GnRH antagonist in the treatment of prostate cancer

Prostate cancer is one of the most common cancers in men, predominantly in developed countries. Currently, some 10-20% of patients are diagnosed with late stage disease and many of these patients will have symptomatic cancer. In advanced prostate cancer the therapeutic options have generally been palliative. During the last few decades, androgen ablation has become one of the most commonly used procedures for such cases, aimed at slowing disease progression and the alleviation of symptoms. GnRH agonists inhibit the secretion of LH and FSH from the pituitary gland. This causes a suppression of testosterone production in the testis. GnRH agonists act through a mechanism of permanent GnRH receptor activation, leading to receptor down-regulation. One of the disadvantages of GnRH agonists is an initial increase of testosterone level; this can lead to an exacerbation of symptoms ("clinical flare"), such as worsening of bone pain, urinary obstruction and spinal cord compression. GnRH antagonists represent another option of reversible chemical castration. Degarelix (a fourth generation GnRH antagonist) has an immediate onset of action, leading to testosterone suppression to castrate levels (serum testosterone level < 0,5 ng/mL) within the first few days after subcutaneous injection. GnRH antagonists competitively bind to the GnRH receptors and cause a rapid decrease of LH/FSH excretion with no initial GnRH receptor stimulation and no clinical flare. In contrast to some GnRH antagonists, the potential risk for clinically significant hypersensitivity reactions is considered to be low. © Dario Cova.