Degarelix: a new approach for the treatment of prostate cancer.
Androgen deprivation therapy remains the mainstay of medical treatment for prostate cancer. Generally, this is achieved with medical androgen deprivation rather than orchidectomy, as most patients find the permanency and psychological effects of the latter unacceptable. Gonadotrophin-releasing hormone (GnRH) agonists are the most widely used androgen deprivation therapy, but do have some drawbacks. The most apparent is the induction of a transient surge in serum testosterone that may stimulate tumor growth, causing patients to experience new or worsening cancer symptoms. These may include increased bone pain and urinary retention, and consequently delay the therapeutic benefit of these agents. These shortcomings led to the development of the GnRH antagonists/receptor blockers. Degarelix is a novel GnRH receptor blocker that has an immediate onset of action, producing a rapid decrease in luteinizing hormone and follicle-stimulating hormone leading to fast testosterone suppression without the initial surge associated with the GnRH agonists. Administration of subcutaneous degarelix depot has been investigated in multicenter, open-label, randomized, phase II trials of up to 1 year's duration in patients with prostate cancer. Degarelix induced rapid luteinizing hormone suppression and fast, profound and sustained suppression of serum testosterone (<or=0.5 ng/ml), with additional rapid and sustained reductions in dihydrotestosterone and prostate-specific antigen. Dose-finding trials indicate that a 240 mg starting dose and an 80 or 160 mg maintenance dose is most effective for long-term testosterone suppression. In a phase III, 1-year comparator trial, degarelix produced fast testosterone suppression and prostate-specific antigen reduction >or=2 weeks before clinically relevant changes were induced by the GnRH agonist leuprolide. Degarelix was as effective as leuprolide at reducing testosterone <or=0.5 ng/ml from 1 month to study end. Degarelix was well tolerated, with uneventful toxicology and no evidence of systemic allergic reactions. This new agent represents an important pharmacological development in the hormonal treatment of prostate cancer.
Persson
Bo-Eric
BE
Ferring Pharmaceuticals, Saint-Prex, Switzerland. Bo-Eric.Persson@ferring.com
Kold Olesen
Tine
T
Jensen
Jens-Kristian
JK
D002986:Clinical Trials as Topic; D064420:Drug-Related Side Effects and Adverse Reactions; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D006801:Humans; D008297:Male; D009842:Oligopeptides / Q000009:adverse effects / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D011966:Receptors, LHRH / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
D009842:Oligopeptides; D011966:Receptors, LHRH; C431566:acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide; D007987:Gonadotropin-Releasing Hormone