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)".
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.
.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.
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.
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).
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 ?
"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."
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?
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.)
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?
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.
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.
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.
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.
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:
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.
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.
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.
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