What is digarelix?
On December 24, 2008, the FDA approved the new molecular entity drug, degarelix, for the treatment of advanced prostate cancer.
Degarelix is an important treatment for prostate cancer and is a new generation GnRH antagonist with high water solubility, no systemic allergy, and no androgen fluctuations. The introduction of this drug has brought a boon to patients with advanced prostate cancer and its clinical application is more convenient.
Indications
For the treatment of advanced prostate cancer.
Mechanism of action
Digarelix is a GnRH receptor antagonist that binds reversibly to the GnRH receptor, reducing the release of gonadotropins and subsequently inhibiting the release of testosterone (androgens) that are essential for the continued growth of prostate cancer, thereby slowing the growth and progression of the prostate.
Dosage
Digarelix is for “subcutaneous administration” only.
- Initial dose: two injections of 120 mg each for a total dose of 240 mg; first maintenance dose given after 28 days of initial dose treatment;
- Maintenance dose: 80 mg in a single injection, administered every 28 days.
What are the benefits of degarelix for prostate cancer?
Prostate cancer is a hormone-sensitive tumor, and the common initial treatment regimen is androgen deprivation therapy (ADT). Depending on the principle of action, ADT can be divided into the following main categories:
- Androgen synthesis inhibitors: e.g., abiraterone, prednisone;
- GnRH agonists: e.g., goserelin, leuprolide, buserelin;
- GnRH agonists: e.g., goserelin, leuprolide, buserelin;
- GnRH inhibitors: such as degarelix;
- Non-steroidal anti-androgen drugs: e.g. bilucamide, flutamide, nilumet;
- Estrogenic drugs: e.g. estramustine phosphate;
- antiandrogenic drugs: e.g., ketoconazole, prednisone.
Gonadotropin-releasing hormone (GnRH) agonists and antagonists have been approved for the treatment of advanced prostate cancer.GnRH antagonists bind directly to the GnRH receptor, blocking the effects of gonadotropin-releasing hormone on the pituitary gland and producing direct inhibition of luteinizing hormone, follicle stimulating hormone, and testosterone. inhibition.
In the future, GnRH antagonists have the potential to replace GnRH agonists as first-line agents in androgen deprivation therapy (ADT).
Treatment does not cause a surge in androgen levels initially
Previous hormonal therapies for prostate cancer were characterized as “up and then down,” meaning that some therapies caused a spike in testosterone levels early in treatment before they became effective and testosterone levels began to decline. This means that at the beginning of treatment, tumor growth is temporarily promoted rather than inhibited, but Degarelix is effective from the start.
Efficacy not inferior to GnRH agonist analogs
An open-label, multicenter, randomized, parallel clinical trial of 610 patients with prostate cancer was given digarelix 80 mg (subcutaneous), 160 mg (subcutaneous), and leuprolide 7.5 mg (intramuscular) as maintenance therapy after initial dose treatment.
The results showed that the proportion of patients in the three groups who maintained depot levels of testosterone during 1 year of treatment was 97.2%, 98.3%, and 96.4%, respectively, indicating that digarelix was not inferior to leuprolide in terms of efficacy.
Digarelix significantly reduces the risk of cardiovascular events compared with conventional GnRH agonists
A European study that meta-analyzed 2328 prostate cancer patients from different countries showed that treatment with degarelix reduced the risk of cardiovascular disease, such as heart disease and stroke, and the risk of death by more than 50% in patients with prostate cancer later in life compared with patients receiving GnRH agonists.
The study also found that patients treated with degarelix had a significantly higher overall survival rate, improved prostate cancer symptoms, a lower probability of fracture, and fewer adverse renal and urinary effects compared to those receiving GnRH agonists.
Likewise, a study at Peking University People’s Hospital showed that both GnRH agonists and degarelix increased the risk of cardiovascular disease in patients with ADT, but patients using degarelix had a lower risk of cardiovascular disease than those in the conventional GnRH agonist group. In addition to this, digarelix caused lower rates of muscle pain than the traditional GnRH group.
Digarelix has been widely used as a first-line treatment in the US, EU, and Japan, but its safety still needs to be supported by more trial data. Currently, the most common adverse reactions reported in clinical studies are injection site reactions (pain, redness, and swelling), hot flushes, weight gain, malaise, and elevated concentrations of certain liver enzymes.