Re Confusion over my next steps re properties and status of my hormone therapy injection.

[Yarris980]

Hi All

About to start my hormone therapy. On bicalutamide and about to take apalutimide and have Zoladex injections. I was handed a leaflet by the consultant at my last consultation two weeks ago, explaining LHRH agonists and GnRH antagonists. After research I have found that Zoladex is a GnRH agonist - so possibly different from these two ? I am told in patients with heart disease / heart failure, agonists may be better than antagonists. However, as the leaflet doesn't seem to be relevant to the treatment I am having, I would like clarification if anyone can help me. In between consultations I can only contact my Oncologist on writing through his secretary, and I am finding it difficult engaging my GP, but will persist. As with the situation for most in the UK, a doctor's appointment has meant dealing with mainly doctors and assistants other than my registered GP, so there is little continuity even though the practice seems good !

Therefore I would like to know how is a GnRH agonist different to the other two mentioned in my leaflet and what are the different implications ?

What are the preferred hormone injections for heart failure/ heart disease, and what the difference is between LHRH agonists, GnRh antagonists and GnRh agonists on this ?

Trying to get my GP to refer me for blood tests and to local specialist Cardio Oncologists, rather than my Cardiologist, so I would appreciate some knowledge before hand.

Thanks in advance

[petabyte]

LHRH = GnRH

Orgovyx has recently been approved in the UK. June last year if i remember correctly. Oncologists probably don't have much experience with it but if you want it, ask for it!

LHRH agonists

the most common e.g. Decapeptyl (triptorelin), Zoladex (goserelin), Lupron/Eligard (leuprolide, very common in the US but not used much in Europe). All of these are long lasting injections or implants (1, 3 and 6 months).

LHRH antagonists.

These are more recent. The first was Firmagon (degarelix), a monthly injection, and now Orgovyx (relugolix) daily pills.

Antagonists tend to suppress testosterone more quickly and it recovers more quickly. They tend to have less cardiac side effects.

[Yarris980 in reply to petabyte]

Noted - many thanks- much appreciated.

[petabyte in reply to Yarris980]

With cardiac issues you should really be on an antagonist. Firmagon requires special skills to inject every 28 days and often has injection site issues. A daily pill is much more convenient if you are sure you can take it every day.

[Yarris980 in reply to petabyte]

Petabyte - does Orgovyx as a pill replace the need for a Firmagon injection or does treatment still involve both ?

[petabyte in reply to Yarris980]

It replaces it. Orgovyx OR Firmagon.

And they will add a second generation anti androgen Erleada (apalutamide).

These are also pills (1 dose of 240mg per day)

Hmm Orgovyx has a major interaction with Erleada... May not be feasible or require a double dose of Orgovyx. Talk to your doctors.

drugs.com/drug-interactions...

[petabyte in reply to petabyte]

This is from observational data so it is not strong evidence,

ahajournals.org/doi/10.1161...

Gonadotropin-releasing hormone agonists had strong positive associations with cardiovascular death, cardiovascular disease, myocardial infarction, and stroke, among the 3 meta-analyses of observational trials

Gonadotropin-releasing hormone antagonists had mixed associations with cardiovascular disease and myocardial infarction and no associations with cardiovascular death and stroke, among the 3 meta-analyses of observational studies.

[petrig]

Ask Orgovyx.

[Yarris980 in reply to petrig]

Hi - looking further into it - what other drug would be needed with Orgovyx as it has major interactions (as petabyte has suggested) with Apalutimide (Erleada) ? Does anyone also know whether your first choice of hormone treatment can inhibit your later choices for other treatment once the original treatment stops working ? Is there an initial treatment that keeps your options open ?

[petabyte in reply to Yarris980]

Treatment is often limited based on what is approved for the cancer stage. These rules are based on many things including trial evidence( and cost ofc).

In theory Apalutamide could be replaced with Nubeqa (darolutamide) or Xtandi (enzalutamide) but it may not be allowed.

But a double dose of Orgovyx (which in the UK is much cheaper than Erleada) could be an option (as noted in the drugs.com link) but monitor testosterone to make sure it is working. Many oncologists don't monitor T, no idea why...

Anyway talk to your doctors.

[Yarris980 in reply to petabyte]

Thanks - much appreciated

[Tall_Allen]

LHRH and GnRH are functionally the same.

GnRH antagonists like degarelix seem to have a better cardiovascular profile than GnRH agonists like goserelin. But unless he has a pre-existing cardiac condition or significant cardiac risk factors, the difference is small and the effect is low.

ahajournals.org/doi/full/10...

pmc.ncbi.nlm.nih.gov/articl...

ascopubs.org/doi/10.1200/JC...

auajournals.org/doi/abs/10....

nejm.org/doi/full/10.1056/N...

[Yarris980 in reply to Tall_Allen]

Thanks Tall Allen - also heard that Antagonists lower testosterone much quicker than Agonists - which may also be a risk to patients with heart failure even though I believe Antagonists are generally safer ?

[Tall_Allen in reply to Yarris980]

I don't understand your points.

[Yarris980]

I’m just wondering whether the sudden testosterone namely 2-3 days with antagonists may also be dangerous for heart failure compared to the more gradual drop occurring with agonists - just trying to balance out all the options…

[PCaWarrior in reply to Yarris980]

T flare from agonists might destabilize plaque in the arteries. Some studies show agonists are preferred to reduce CVD risk. Some show antagonists are better.

I've never heard that a quick drop in T exacerbates heart failure.

If it were me I'd focus on testing and monitoring. And potentially a statin if MO agrees.