No More Orgovyx, Continuing with Abiraterone and Prednisone

[rmarkley]

My MO and I have just decided to try the methodology reported in the study titled:

"Suppression of testosterone production using abiraterone acetate (AA) with or without androgen deprivation therapy (ADT) in metastatic castration resistant prostate cancer (mCRPC)".

Here is a link to the study:

ascopubs.org/doi/abs/10.120...

My prostate cancer details are as follows:

Prostate cancer, stage IIA, T1c N0 M0, Gleason score 7, now with metastasis to bones. (2 small spots on left hip)

My medication history is:

1/26/2015 – Focal Laser Ablation (FLA) PSA 4.9

10/7/2019 – repeat FLA PSA 16

6/8/2020 FLA 32

6/24/2020 Axumin Pet/CT scan

6/26/2020 Bone Scan Whole Body

7/14/2020 ADT Started – Firmagon, monthly

8/5/2020 Dexa Scan

8/11/2020 Zytiga -250 mg, prednisone 5mg daily continuing until now

9/1/2020 SpaceOAR Insertion

9/8/2020 – Xgeva – 120 mg - every 12 weeks

9/16/2020 – 10/13/2020 – radiation

10/27/2020 PSA <0.04 – continuing until now

10/27/2020 testosterone level - <7.0 continuing to present

7/12/2021 cancel Firmagon

7/13/2021 – Orgovyx daily until now

There was a discussion that included this subject area recently. Here is a link to it:

healthunlocked.com/advanced...

Read the replies.

I am interested in folks opinions on this methodology.

Note that I am still castrate sensitive.

[LearnAll]

I am glad...finally there is a study telling us that Abiraterone alone is capable of working effectively as ADt. I have been only on Abiraterone for last 1 year intermittently with full Testosterone suppression during on periods (Total T less than 5) My last Lupron was in Dec2019,.2 1/2 years ago. This study makes me even more comfortable to keep going without any lupron like meds.

[rmarkley in reply to LearnAll]

Thanks. I have 1 more Orgovyx to finish. I start Abi and pred only on Monday-June 6, 2022.

[LearnAll in reply to rmarkley]

Because only Abi treatment was my experiment, I have been measuring Total T and Free T every 2 weeks for last one year, paying out of pocket.

[rmarkley in reply to LearnAll]

.My MO has ben measuring T every 6 months. I will have to ask him to measure Total T and Free T at least every 30 days for a while until we see how this new (to me) program works.

[rmarkley in reply to LearnAll]

Do you bother with checking your PSA? Mine gets checked every 6 weeks. My T gets checked every 3 months or so.

[LearnAll in reply to rmarkley]

I check PSA and T both every 2 weeks from paying out of my own pocket. Insurance allows PSA and T only once in 3 months.

[rmarkley in reply to LearnAll]

If you don't mind, what are your typical levels of T and Free T?

[LearnAll in reply to rmarkley]

On May 17,22...Total T= 4 ng/dL, Free T= 0.3 . This is with 250 mg Abi with evening moderate fatty meal (about 10% fat)

[6357axbz in reply to LearnAll]

Yes! Interesting. My MO discontinued my Lupron three months ago and I remain on Abi only. I still am castrate sensitive.

[dhccpa in reply to 6357axbz]

You guys have pitme in the mood to bring this up with my Doc.

[noahware]

Both my Dana Farber MO and his PA approved of the idea of abi monotherapy. (It was in the back of my mind all along, but the PA suggested it as a possibility even before I mentioned it to them!)

Unfortunately, my ADT+abi kept me castrate but I had PSA progression prior to getting a chance to see how I would do on abi alone. To my docs and me it seemed that time to castrate resistance or PSA progression would not be impacted by dropping ADT from the abi+pred regimen, since abi is already doing what ADT does, plus more.

One thing to consider is the idea of adding dutasteride to the abi monotherapy, as there has been some discussion on the forum about the potential for metabolites of abi to feed PC progression. (My MO had just agreed to add it when my abi failed.) That may be worth researching or reviving with a new thread.

[Seasid in reply to noahware]

Could you change to Nubequa? Than you would get rid of the Prednisone and Abiraterone and you would not need to add dutasteride when Abi fails?

[noahware in reply to Seasid]

The point is not to add dutasteride after abi fails, but to add it prior to failure, so that abi is more effective. The metabolites of abi that might feed PC do not necessarily mean abi has failed or is failing, but possible just that abi is doing some harm as well as some good. (And still doing far more good than harm.) So more of a potential safeguard.

When abi is actually failing, I think it is possible to change from pred to dex, to get more mileage out of it. There is also another med, I believe, that was developed to proloing effectiveness of abi.

I chose to just drop the abi/pred and enter a Lu-177 trial. If I had gotten into the other arm, yes, I would have been switched to an antiandrogen (but it would have been Xtandi [enzalutamide], not Nubequa [darolutamide] as the alternative).

[LearnAll in reply to noahware]

Abi blocks ALL 3 sources (factories) of testosterone production viz. Testicles, Adrenals and cancer cells. Testicles are the main production factory (like the Azov steel plant) So when all 3 sites are block by Abi, the testosterone production falls dramatically causing below 10 T Level in most men.Problem is that the some leftover T still keeps on converting to a very strong form of T called DHT (DiHydroTestosterone) and this stronger version can keep stimulating the cancer cell growth. The solution is to block this form of T (meaning DHT). As dear noaware stated above. This is done by using Finasteride or/and Dutasteride along with ABI. This combination of Abi+ Duta ensures almost total blockade of T and also DHT choking cancer cell growth .

noahware, will you please elaborate on other metabolites of Abi which you indicated above ?

[noahware in reply to LearnAll]

Coincidentally (or not), somebody just posted a reply on a thread I started, regarding this very thing, some months ago:

healthunlocked.com/advanced...

"In a paper published in June of 2018, a team led by Nima Sharifi from the Cleveland Clinic identified that certain metabolites of abiraterone are AR agonists. As such, abiraterone metabolism creates its own competitor, in a manner of speaking... [by producing] 3-keto-5-beta abira abiraterone [which] ends up as an androgen agonist, thus potentially mitigating the antitumor potency.

The enzyme that catalyzes the conversion of D4 abiraterone to 3-keto-5-alpha abiraterone is 5 alpha reductase, the very enzyme that could be catabolized by the addition of a 5 alpha-reductase inhibitor such as finasteride or dutasteride. Although such treatments have not resulted in substantial antitumor activity, they have not been studied in this context.

One possibility is that we could combine abiraterone with 5 alpha reductase inhibitors. This has been done on a small scale but not based on the genetics of polymorphisms."

[MateoBeach in reply to noahware]

This is so very interesting. Dutasteride blocking conversion of AA to 3k5a-AA stimulating ARs being the problem more than residual DHT. It would also suggest that, if 250 mg AA is sufficient to maintain very low castrate T, then the 1000 mg dosing might be detrimental in providing more AA for conversion. The key to implementing is individual monitoring through regular testing, of course. Adding dutasteride might also extend useful life of AA+P?

[noahware in reply to MateoBeach]

Not sure if it would extend useful life, but maybe just increase efficacy. Having failed abi+pred, I am most interested in things that might help restore effectiveness such that I could return to abi after Lu treatments are over. (As for as prolonging effectiveness while still sensitive, I think LearnAll is on the right track with intermittant use.)

[Seasid in reply to noahware]

I think professor L. Klotz from Toronto explained that in his YouTube video. He recommended to also add statins, metformin and a use of Degarelix. I am following his recommendation but without Abi. I have to make some decisions very soon as my PSA is 0.65 now. I believe that the Nubequa is the best but it is hard to get. Ok. Ensalutamide iz also very effective but it is crossing the blood brain barrier and could cose falls. Can you explain please in more details we why would not you take Nubequa?

[Seasid in reply to Seasid]

Sorry, Professor Laurence Klotz. My memory failed me. uofturology.ca/directory/fa...

[Seasid in reply to Seasid]

Here is some video about Degarelix (firmagon). Useful if you have heart problem or if you wish to avoid it in the future as 30% of pc patients end up with heart problem.

[Seasid in reply to Seasid]

youtu.be/J2J1zuPzmus(Not working as expected?)

[GP24]

Here is a completed study testing Abiraterone+P without ADT:

nature.com/articles/s41391-...

[rmarkley in reply to GP24]

Thank you for providing me with this more recent trial. I will pass this along to my MO. I am and he will be encouraged by the trial results.

[LearnAll]

smurtaw, rising T while on Abiraterone is scientifically inaccurate. Abi blocks all 3 sources of testosterone production. This poster may be an anomaly as his Cyp17 enzyme system may be malfunctioning causing Abi not to do its job.

[MateoBeach]

Thanks for this posting rmarkley. I’ve been wondering why so few have tried this. Habit from the trials that have only looked at additions to ADT, Ended up grouping AA with the advanced AR drugs which are entirely different than CYP3 inhibitors. Inky nagging question for me is whether or not the resulting high LH levels might make some mischief in mutated PC cancer cells.

[MateoBeach in reply to MateoBeach]

Correction AA is CYP17 inhibitor, not 3. Rate limiting first step in androgen synthesis

[Seasid]

Sorry, but I didn't understand why would you stop ADT? Is that what you are concydering? I am taking Degarelix and concydering adding maybe Abi and prednisol. Why would I experiment with stopping ADT? Not many people do. Better add statins. Otherwise at some point your cancer will start producing testosteron from by the cancer accomulayted cholesterol and your testosterone levels will start rising.

[Seasid in reply to Seasid]

My last testosterone level was 0.3. i was positively surprised as my testosterone levels can go up and down.

[rmarkley in reply to Seasid]

There have been a few studies that show T control is as good on Abiraterone and prednisone only. There appeared to be minimal usefulness to including an agonist or an antagonist. One recent study is:

nature.com/articles/s41391-...

Another earlier study is ascopubs.org/doi/abs/10.120...

A number of the replies to this thread indicate that this technique is approve by a number of high ranking MO's. Also blessed by Dana Farber Cancer Institute. My MO consults with them.

[Seasid]

I also don't want. It is too experimental for me. I am happy with my Degarelix. I understand the reason to try but i am not volunteering. I am happy with my 0.3 testosterone with Degarelix plus 40 mg Crestor.

[Seasid]

Can you feel out your health profile better? Your age is also important here.

[noahware]

You ask "I've been using AA for over 3 years. Why is it still supposedly working for me?"

Do you mean working to keep T low, or working to keep PC at bay?

In all of the studies I've read or seen referenced, abi alone keeps nearly all men at very low T levels. (In any drug that is self-administered, as you note, there is of course a chance of non-compliance or imperfect dosing.)

I am curious as to how many men your MO put on abi without ADT, as this is not generally accepted SOC. My MO was quite sure that abi alone would do the trick for most men.

[Seasid]

Very useful information. Thanks