Degarelix Shows Promise as Second-Line Hormonal Therapy for Men With Prostate Cancer

When Degarelix (FIRMAGON) which is a gonadotrophin-releasing hormone (GnRH) receptor blocker was first approved by the Food and Drug Administration (FDA) I contacted Ferring Pharmaceuticals and spoke with their medical director. I asked if Degarelix could be used as a second line hormone therapy drug after the traditional first line GnRH agonist drugs (Lupron etc.) failed. At that time, he told me there had not been any research on that question. I hung up the phone feeling very disappointed.

The good news is that in Barcelona, Spain on April 17, 2010 there were study results presented that showed that Degarelix could stabilize or reverse disease progression in men with prostate cancer after failure of the traditional GnRH agonist treatment The study was presented by researchers at the 25th Annual European Association of Urology (EAU) Congress.

Simply put, the results demonstrate that degarelix maintained prostate-specific antigen (PSA) suppression and lowered luteinising hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels.

Kurt Miller MD, Department of Urology, Charité Universitätsmedizin Berlin, Berlin, Germany, discussed the 3-month results of this open-label, exploratory, multicentre study exploring the utility of degarelix as a non-cytotoxic second-line therapy for prostate cancer with signs of hormone resistance.

This study, which was very small including only 25 men with histologically-confirmed prostate cancer who had experienced PSA progression despite at least 1 year of treatment (mean duration, 4.1 y) with a GnRH agonist. They defined PSA progression as 2 consecutive 50% rises in PSA above nadir at least 2 weeks apart and at least 1 PSA value of >=2.5 ng/mL in the last 6 months of treatment. Most of the participants had locally advanced (44%) or metastatic (28%) disease and a Gleason score of 7 to 10 (76%).

The subjects received an initial dose of degarelix 240 mg followed by monthly maintenance doses of 80 mg (standard dosing), all given by subcutaneous injection. Stabilization of PSA was defined as a relative change from baseline not exceeding 10% after 3 months of treatment.

• At month 1, there appeared to be 8 responders; however, 4 men (16%) achieved the primary endpoint. One man had castrate testosterone at screening but a borderline testosterone value and high LH at entry. A second responder had castrate testosterone but measurable LH at entry, while the remaining 2 responders had castrate testosterone and undetectable LH.

• PSA doubling time was prolonged in 64% of men (n = 14).

• LH was undetectable in 88% (n=22) of men after the switch to degarelix.

• FSH levels fell in 84% of men and testosterone levels decreased in 40% of the men (n = 10).

• Some men appeared to have a late response (>3 mo) to degarelix.

A total of 60 adverse events were reported by 18 men (72%); most were mild (n = 14; 56%) or
moderate (n = 8; 32%), and 1 man discontinued due to treatment.

Additional research to confirm these results is needed. However, if I were in a position that I was becoming hormone refractory I would insist that my doctor try using Degarelix prior to my moving on to any other treatment.

Funding for this study was provided by Ferring Pharmaceuticals.

Presented at EAU