The luteinizing hormone-releasing hormone (LHRH) antagonist drug degarelix (Firmagon) is sometimes used for initial ADT instead of the LHRH agonist drugs like Lupron, Eligard, and Zoladex. For prostate cancer patients who first present with symptoms of metastatic disease, physicians will often start them on Firmagon. Firmagon, unlike the LHRH agonists, does not cause the ‘clinical flare’ in symptoms (e.g., bone pain) that’s linked to an initial surge of testosterone at the onset of treatment. Firmagon also kicks in more quickly than the LHRH agonists do. However, it is administered as a depot injection that lasts only a month, and it is more likely than LHRH agonists to lead to inflammation at the injection site.
But what of other side effects? In this succinct review, Drs. Freedland and Abrahamsson summarize six studies on the side effects of Firmagon. They conclude that for patients with pre-existing cardiovascular disease the chance of a serious cardiovascular event, such as a heart attack or stroke, is reduced by more than half in the first year of treatment for patients on LHRH antagonists compared to patients on the standard LHRH agonists.
A head-to-head, direct comparison between Firmagon and the various agonists, examining all known side effects, has not been undertaken. However, Freedland and Abrahamsson suggest that the risks of other serious side effects, notably metabolic syndrome, diabetes, cognitive impairment and depression, are likely to be the same between the two classes of drugs. The authors go on to speculate that Firmagon may be better for bone health, but they acknowledge that clinical data are lacking to confirm this.
It should be noted that this review was funded by Ferring, the company that markets Firmagon. It is thus in their best interest to have reports out showing the benefit of their drug versus other drugs like Lupron, Eligard and Zoladex, which currently have the largest share of the North American market.
Interestingly, Ferring may soon be facing a new competitor. Relugolix, which is an oral LHRH antagonist, is currently up for FDA approval in the USA. Because it is an oral drug, it does not require injection and therefore doesn’t cause local inflammation at the injection site like Firmagon does.
Relugolix has already been shown to be as effective in suppressing testosterone as drugs like Lupron. It will be interesting to see the outcomes of direct comparisons between the two LHRH antagonists, the injectable Firmagon and the oral Relugolix, in terms of overall side effects.
To read the study abstract, see:
https://pubmed.ncbi.nlm.nih.gov/32655041/
Freedland, S.J. & Abrahamsson, P.A. (2020). Androgen deprivation therapy and side effects: are GnRH antagonists safer? Asian Journal of Andrology. Epub ahead of print.