Taking zytiga with daralutamide

[cwoodland]

anyone taking a combo of zytiga and daralutamide?

[JohnInTheMiddle]

You asked if anyone is taking a combination of Abiraterone (Zytiga) and Darolutamide (Nubeqa) in circumstances of hormone therapy for metastatic prostate cancer.

The answer is probably no, because this combination is not part of any recommended recipe from any of the big randomized control trials that have shown very positive results.

Just to put this in context, if you did this you would always first be taking an ADT drug therapy (either an agonist or an antagonist), which is the foundation of all prostate cancer therapy.

So now what about your proposed combination? I do recall reading some paragraph in a paper once that this sort of combo thing was tried, and was found to be not helpful or superior to just regular doublet or triplet therapy. And on the downside you also have the side effects from both drugs.

It's interesting to note how the three different types of hormone therapies all work together to stop testosterone from reaching cancerous prostate cancer cells. We know this of course as castration. And our cancer is held at bay as long as our cancer still depends on testosterone - in other words we are still "castration sensitive". (Of course all this is beside the point if our cancer becomes "castration resistant" ...)

1. The ADT hormone therapy shuts down requests for testosterone manufacturing from a pathway sort of starting in the brain in the pituitary. I think of this as "the top". We all start with ADT and probably we never stop. But unfortunately ADT won't necessarily completely stop the testosterone manufacturer in the body. So we have discovered of course that there are more things we can do.

2. Abiraterone stops the manufacture of testosterone from cholesterol, everywhere. The body is no longer receiving requests for testosterone because of ADT shutdown, however some testosterone might still be manufactured. This category of hormone therapy is called ARPI or "androgen receptor pathway inhibitor". In terms of the body's testosterone life cycle, I think of this as "in the middle".

3. There's a third way to stop prostate cancer cells from getting any testosterone signaling, thence to do their wicked work. This method is to jam up the testosterone receptors that are on the surface of all the prostate cancer cells. Darolutamide and similar drugs jam up these receptors so that any residual testosterone can't actually meet up with a prostate cancer cell. This category of prostate cancer therapy drug is called an ARi or "androgen receptor inhibitor". I think of this as "at the bottom".

So, the successful recipes for metastatic prostate cancer hormone therapies that we are talking about are either (1) ADT + ARPI or (2) ADT + ARi. Both combinations are called doublet therapy (let's ignore the Prednisone for now). And if you had Docetaxel chemo to either one you get triplet therapy. In many cases triplet therapy is the gold standard today and presents a much extended life expectancy.

As I mentioned earlier, no one puts ARPI and ARi together. There's no additional benefit apparently and there is the downside of combo side effects.

Question for you is "why you were asking the question"? I'm assuming you're not self-medicating but that you have a medical oncologist.

[cwoodland in reply to JohnInTheMiddle]

thank you for the detailed response. My question is based from a recommendation by a medical oncologist I recently visited.

[JohnInTheMiddle in reply to cwoodland]

Please share more about this when you are able to, CW. Is there new research that shows (ADT + ARPI + ARi) all together are effective? And tolerable? And how does chemo fit into that?

[ARIES29 in reply to cwoodland]

Hi cwoodland, I have been on this combination for 10 months? now & it has reduced the PSA to 0,5 from 4.6. However the Oncologist put me on 1200mg/day or 4 tablets, it had SE so have reduced it to 600mg day or 2 tablets with the usual Zoladex every 3 months.

Hope this helps & I am in Australia.

[JohnInTheMiddle in reply to ARIES29]

ARIES29: From your bio and your reply here, you are not on a combination of ADT + ARPI + ARi. You're on standard doublet therapy with an ADT GnRH agonist (Zoladex/Goserelin) and androgen receptor inhibitor (Nubeqa/Darolutamide). Good news: your ADT + ARi combo is right up to date as a therapy recipe supported by powerful research.

[ARIES29 in reply to JohnInTheMiddle]

Good to know, Thanks.

[Seasid in reply to cwoodland]

Who is your medical oncologist?