Effective use of Firmagon (degarelix) for advanced prostate cancer

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Effective use of Firmagon (degarelix) for advanced prostate cancer



Firmagon (Degarelix powder) is a competitive, reversible GnRH receptor blocker, for patients with advanced hormone-dependent prostate cancer. Where Injection technique is critical; Nora Sullivan, a specialist nurse at Hibernian Healthcare, explains that very slow injection (over two or even two and a half minutes) is the key to minimising the risk of injection site reactions.

by Christine Clark: Prostate cancer is now the most common cancer in Europe for men and the third most common cancer overall. Some 417,000 new cases were diagnosed in 2012(CRUK1) and there were just over 92,000 deaths. (CRUK 2a) In the UK, about 30 men die from prostate cancer every day and the majority of deaths are in the over-75 age group. (CRUK 2b) However, survival has improved considerably. Forty years ago, more than two in 10 men diagnosed with prostate cancer survived their disease for at least ten years, now it is more than eight in 10. Much of this increase is attributed to earlier and wider detection of prostate cancer as a result of the use of the tumour marker, prostate specific antigen (PSA). (Ref CRUK 3) Prostate cancer is more common in older men, those with a family history of prostate cancer and in black African and Afro-Caribbean men. (CRUK 5)

Advanced prostate cancer describes locally invasive disease (tumour stage T3 or T4) or metastatic disease. Locally invasive disease can cause obstructive uropathies and one of the problems of spread of disease to bones can be spinal cord compression. The American Joint Committee on Cancer (AJCC) TNM system is used to determine the stage of the disease. It is based on five pieces of information – the extent of the tumour (T), whether it has spread to lymph nodes (N), the presence of metastastis (M), the PSA level at diagnosis and the Gleason score (based on prostate biopsy findings). (Ref American Cancer Society)

Androgen deprivation therapy (ADT) is one of the key elements of treatment for advanced prostate cancer. The rationale for this is that testosterone is essential for the growth and proliferation of prostate tumours. ADT results in regression of androgen-dependent tumours. For many years ADT has relied on either orchiectomy or treatment with long-acting gonadotrophin releasing-hormone (GnRH) analogues. These measures still form part of modern treatment pathways (Ref NICE, European Association of Urology guidelines) but are not without problems. Orchiectomy results in a rapid fall in testosterone levels but can be associated sexual dysfunction and negative psychological effects. GnRH agonists cause an initial surge in luteinising hormone (LH) and follicle stimulating hormone (FSH) levels and a corresponding increase in the level of testosterone. Chronic exposure to a GnRH agonist results in down-regulation of GnRH receptors and androgen suppression. The initial surge can be associated with tumour growth and a ‘symptomatic flare’ that can involve worsening bone pain, urinary obstruction, spinal cord compression and fatal cardiovascular events as a result of hypercoagulability. (Ref Drudge-Coates p87a) The clinical effects of a flare may be prevented by pre-treatment with an antiandrogen. (Ref Drudge-Coates p87b) The recently-introduced, direct-acting GnRH blocker, degarelix, which does not cause an initial surge, may offer some advantages.

Degarelix is a competitive, reversible GnRH receptor blocker. It reduces the release of LH and FSH and brings about a rapid suppression of testosterone to castrate levels (<0.5ng/ml) without provoking a surge or flare of symptoms. (Ferring SPC, sect 4.2) A 12-month, randomized, comparative study investigated the efficacy and safety of two different degarelix monthly dosing regimens with a starting dose of 240 mg (40 mg/ml) followed by monthly subcutaneous doses of 160 mg (40 mg/ml) or 80 mg (20 mg/ml), in comparison to monthly intramuscular administration of 7.5 mg leuprorelin in patients with prostate cancer requiring androgen deprivation therapy. (Ferring SPC, sect 5.1) The results showed that testosterone levels fell to castrate levels in 96% of patients in three days whilst in the leuprorelin group there was an initial rise in testosterone levels followed by a steady fall over the next 10 days.