Degarelix: rapidly lowering testosterone in prostate cancer
Clinical review pending
Degarelix blocks GnRH receptors and lowers testosterone without an initial surge. Its mechanism, use and side effects.
What is degarelix?
Degarelix, sold under the brand name Firmagon, is a synthetic peptide made up of ten amino acids. It acts as an antagonist, blocking the receptor for gonadotropin-releasing hormone, or GnRH. Agonists such as leuprorelin and goserelin initially stimulate the pituitary gland before suppressing its activity. Degarelix blocks the receptor from the first dose. Ferring developed it under the code FE200486; it was approved in the US in 2008. Source
How does degarelix work?
Degarelix binds reversibly and competitively to GnRH receptors in the pituitary gland. This blocks the signal that normally triggers the release of luteinizing hormone and follicle-stimulating hormone. These gonadotropins fall within hours, and testosterone reaches castration levels within days. Because degarelix blocks the receptor directly, it does not cause an initial testosterone surge. Additional antiandrogen treatment to protect against this “flare,” as used with GnRH agonists, is therefore not required. Source Source
In advanced prostate cancer, lowering testosterone deprives hormone-sensitive tumor cells of an important growth signal. In the phase 3 CS21 trial, degarelix was noninferior to leuprorelin at maintaining testosterone at or below castration levels over 12 months 1. Testosterone and PSA fell faster with degarelix in the first few weeks. Its rapid onset without an initial hormone surge is an important clinical difference. Source
Is degarelix FDA-approved?
The FDA approved degarelix in 2008 for advanced prostate cancer 2. It is injected under the skin. An initial dose is followed by a maintenance dose every 28 days.
What is degarelix prescribed for?
Degarelix is used for advanced, hormone-sensitive prostate cancer. Rapidly lowering testosterone without an initial rise is particularly important when hormone levels need to fall quickly, for example in people with pronounced symptoms or a high tumor burden. Source
What side effects are possible?
Citing the prescribing information, the source text lists the following common side effects:
- Injection-site reactions such as pain, redness and swelling, particularly after the initial dose
- Hot flashes
- Weight gain and fatigue
- Elevated liver enzymes
Other important risks include:
- QT-interval prolongation on an ECG: particular caution is needed with other medicines that prolong the QT interval or with electrolyte disturbances.
- Hypersensitivity reactions
- Loss of bone density during long-term androgen deprivation
References cited in the source text
Sources: FDA prescribing information for Firmagon; the CS21 phase 3 trial (Klotz et al., BJU International, 2008, DOI: 10.1111/j.1464-410X.2008.08183.x 1), indexed on PubMed.
Provenance and editorial review status
Adapted for Nutrient Desk from the source article. The claims and source attributions in the original text still require clinical review. This draft has not been cleared for indexing.