vials containing 80 mg and 120 mg as powder for reconstitution
Approved indication: prostate cancer
Australian Medicines Handbook section 14.3
Androgen deprivation is one approach to the treatment of prostate cancer. This can be achieved by using agonists of gonadotrophin releasing hormone such as goserelin and leuprorelin. Although these drugs cause an initial surge in testosterone, long-term use leads to decreased production.
Degarelix reduces testosterone production by antagonising gonadotrophin releasing hormone. By blocking the pituitary receptors, degarelix cuts testosterone concentrations within a few days, without the surge seen with gonadotrophin releasing hormone agonists.
In a dose-ranging study, 127 patients were randomised to take a starting dose of degarelix followed by monthly maintenance doses. Within three days the testosterone concentration had fallen into the target range in 89% of the men. Low levels were maintained in most of the 87 men who completed the one-year study. Prostate specific antigen was also reduced.1
Degarelix has to be given by subcutaneous injection into the abdomen. A depot is thought to form at the injection site so that the drug is slowly released. The half-life of the maintenance dose is estimated to be 28 days. Most of the dose is metabolised by hydrolysis and excreted in the faeces. The dose does not have to be adjusted in patients with mild to moderate renal or hepatic impairment.
Degarelix has been compared with intramuscular leuprorelin in a 12-month study. The 610 men in the study had prostate cancers ranging from localised to metastatic. Those who were randomised to take degarelix were given 240 mg followed by monthly maintenance doses of 80 mg or 160 mg. The desired testosterone concentration was achieved by 97–98% of the degarelix groups and 96% of the leuprorelin group.
The reduction in testosterone was more rapid in the degarelix groups. A similar pattern was seen with the reduction in prostate specific antigen.2
Adverse effects are common with degarelix. In the comparative study, 40% of patients had injection-site reactions with degarelix. Less than 1% of the leuprorelin group had injection-site reactions. Other adverse effects reported in the trial included flushing, weight gain and altered liver function. Adverse events resulted in approximately 7–9% of the degarelix group and 6% of the leuprorelin group discontinuing treatment.2During treatment with degarelix the QTc interval on the ECG can be prolonged and some patients will develop anaemia. Some patients develop antibodies to degarelix although it is yet unclear whether this affects long-term efficacy. Although androgen deprivation has metabolic effects, lipids other than cholesterol, and glucose were not studied. Hypercholesterolaemia occurred in 5% of patients given degarelix.2
It appears that an antagonist of gonadotrophin releasing hormone is as effective as an agonist in reducing testosterone concentrations. While at first the reduction is more rapid than with leuprorelin, after about a month there is no significant difference between treatments. Further study will be needed to see the effect of degarelix on survival and whether it has any role in patients who have not responded to a gonadotrophin releasing hormone agonist.
The Transparency Score ( ) is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.
- Gittelman M, Pommerville PJ, Persson BE, Jensen JK, Olesen TK; Degarelix Study Group. A 1-year, open label, randomized phase II dose finding study of degarelix for the treatment of prostate cancer in North America. J Urol 2008;180:1986-92.
- Klotz L, Boccon-Gibod L, Shore ND, Andreou C, Persson BE, Cantor P, et al. The efficacy and safety of degarelix: a 12-month, comparative, randomized, open-label, parallel-group phase III study in patients with prostate cancer. BJU Int 2008;102:1531-8.