I haven't really seen anything on this since Patrick (pjoshea13) had written about it a few years ago: healthunlocked.com/advanced...
Has anyone discussed it with their docs? I plan to, later this week. I guess a few small trials are tentatively showing a potential benefit? I just stumbled upon this editorial, too, which I severely edited down to mostly plain English below, lol: urotoday.com/center-of-exce...
"Recall that abiraterone is not a complicated molecule, it is simply a slightly altered version of progesterone, a naturally occurring hormone.
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."
Written by: Charles Ryan, MD, B.J. Kennedy Chair in Clinical Medical Oncology, Director and Professor of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, Minnesota -- Published Date: July 11th, 2018
Patrick (pjoshea13) has also written about the potential benefits of 5a-reductase inhibitors coming with potential RISKS, too. But doesn't it seem to make sense to use one with long-term abiraterone treatment?
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Noahware, I have been using Dutasteride 0.5 mg once a day along with Intermittent, Adaptive therapy with Abiraterone for last one year. Prior to that, I was using Finasteride for a year along with Intermittent Bicalutamide therapy. My last Lupron inj was 2 years and 2 months ago.Like Guru Nal said..and I agree.. Finasteride and Dutasteride prevent conversion of T to DHT and DHT is the strongest form of T. DHT stimulates prostate cancer cell growth much faster compared to T.
I would like to know why Nalakrats uses both Finasteride and Dutasteride ? Isn,t Dutasteride alone is sufficient as it works on both pathways of DHT formation. ? What is the rationale of using both Finasteride and Dutasteride together ?
Duta is about 95% effective. Fina is about 80% effective. I used both of them during SPT. I'm doing a BAT program now and use fina (duta has an extremely long half life). I'm still trying to get some clarity on the timing and use issue. By itself, duta appears to be a good monotherapy (DART trial). But how does it play with high testosterone and double strand breaks and ca ion influx? Different doctors and research leads me to yes or no.
I used them at the same time. Perhaps more effective. Fina uptake is fast. In retrospect perhaps I could have used both for a few months and then dropped fina. But I didn't notice any sides and my doctor didn't disagree with what I did.
"The main difference between finasteride and dutasteride is that finasteride is selective for type II 5AR while dutasteride inhibits both type I and type II.
Dutasteride not only blocks both types of receptors but also does so much more effectively. This may be a result of the much longer half-life of dutasteride compared to finasteride (~4 weeks vs. 6-8 hours respectively). Dutasteride has been shown to be 3 times more potent than finasteride at inhibiting type II 5AR and more than 100 times at inhibiting type I 5AR. Furthermore, oral dutasteride decreases serum DHT concentrations by up to 90% while finasteride only reduces DHT by 70%."
• in reply to
Also, duta is harsher. Yeah, to reduce liver burden I should have dropped fina. Oh well. 20/20. And perhaps fina/duta is better than duta for other reasons? Prob not but makes me feel better...
So the only reason I can think to prefer finasteride is if you might want to quit it in a hurry... if there is any conceivable reason to want to cycle your 5ARI in an "on/off" way?
I wish I knew. Perhaps during BAT (I've been doing BAT for 5 months). RCTs don't use 5ARIs so I've only been using Fina only during my ADT phase and stop a week before the high testosterone.
Thanks, LearnAll.... can you refresh me on how you are timing the off/on cycles of your therapy? I plan to also discuss this with my MO, as I remain convinced that to stay on abi indefinitely is to invite a quicker onset of treatment resistance (and a transition from CS to CR as the prevailing type of cancer cell)!
Let me know what your MO says. Mine said that we just don't know. She said that it is possible (although not probable) that pulsing AA could hasten resistance. Or perhaps you'd get resistant at the same time but you wouldn't have used AA as much. Or maybe you don't become resistant as fast. Yup, she covered all bases
Noahware..I follow Moffit Center Researchers model... Its not based on timing ...Its based on level of PSA. I have set two points which indicate switching point...My upper set point is PSA 10 and my lower set point is PSA 4. In their research papers, Moffitt guys have used these two set points( i.e 4 &10)I start Zytiga 250 mg a day with a teaspoon of Ghee (liquified butter) when my PSA reaches 10 or crosses 10 upwards. Every 2 weeks I check PSA and total T. Once PSA comes at or below 4, I stop Zytiga. This cycle has repeated for over 10+ times.
When Off zytiga, my T bounces up in 300-350 range...only to go below 10 after being back on Zytiga. So far so good. I hope this continues as I am very happy with the way I am doing...almost zero side effects. Besides I eat a lot of PI13 K inhibitor herbs and foods such as Ginger, Garlic, Red onion, Turmeric, organic sulfur powder, Black seed oil, Munakka Grapes, Cauliflower, DIM, apples, tomato soup every evening, a bunch of herbs like Holy basil, Rosemary, Oragano, Thyme, Sage (a pinch of each one in a cup of fat-free Yogurt. Absolutely no animal fat or animal protein. Lastly, I have 5 miles long brisk walk every single day.
BTW, I do not require any prednisone with my current Adaptive, Intermittent therapy.
That last bit is very interesting... no pred? How does that work?
I realize that PSA, not duration, is the trigger used in most reseach for off/on... I was just wondering what the time of your cycles ended up being. It sounds like about a month or so? (What is the typical duration of "off med" as you move up over PSA 10, and how long does it typically take "on med" to get back below PSA 4?)
I have only read a Gatenby paper on his trial of CR patients who maintained ADT during the abi cycles... are the Moffit guys using this with or w/o ADT, and on patients who are not CR? Do you have any links? Thanks!
EDIT: I just realized... Moffit IS the Gatenby group. So I gather you are extrapolating from their observations, and applying the principles while still hormone sensitive... just as I am thinking! My big question is, how would one pick a baseline if one is not CR, and what is the basis of the "50% drop" as the right time to withdraw abi? (In other words, how did you arrive at PSA 10 and PSA 4 as your set points with a good degree of confidence?)
Moffit Center guys are Dr.Gatenby , Dr.Zhang and others who has propounded the model of "ADAPTIVE" intermittent therapy. I decided to test the basic premises of their model on myself.. although I am androgen sensitive (CS). I do blood checks every 2 weeks. My On cycle is approx. 14 to 16 days and Off Cycles are also almost as long as On cycles. PSA fluctuates from a low of 2.0 to high of 12-14.I had Lupron for first 9 months (3 inj) when I received the diagnosis. My last Lupron was on Dec04,2019. Nadir PSA was 0.19.
I am taking risk and so far it is rewarding me with excellent quality of life. I am not using 50% drop formula. In one of Dr Gatenby's paper, they were using PSA 4 and PSA 10 as set points and I just started imitating them.
As we all know that Intermittent therapy has been proven to be NON-Inferior to continuous ADT. But the truth is that we have to be very very careful in selecting who is eligible for Adaptive Intermittent ADT. Men with Germline mutations, Gleason grade above 4+4, Visceral mets, High LDH and neuroendocrine biomarkers are some examples of men who should never consider intermittent ADT as it can be too risky.
A carefully screened population of men by biomarkers, scans, pathology and clinical status ,high physical performance level can try Adaptive IADT with very close monitoring. MOs may not agree in most cases as it is still not mainstream...and costs are higher because Insurances may not cover frequent tests. Last but not the least, one has to be very disciplined with what he is eating and maintain high level of physical exercise during this type of therapy.
Thanks for all the comments so far. Just to be clear, I am not talking about the use of a 5ARI to inhibit DHT along with your ADT hormonal therapy, which of course has long been advocated by some (Snuffy Myers, Bob Liebowitz) well before abiraterone came along.
Rather, I was referring to the more recent discovery that abi metabolizes into compounds that, one of which, might serve to PROMOTE tumor progression in some men. So use of a 5ARI to address that potential could only have arisen in the past five years or so, and would be unrelated to the original rationale for adding a 5ARI to your therapy.
So I am wondering two things: 1) have any of you guys discussed this (recently hypothesized) possible downside to abi therapy with your docs, of abi acting partly as a tumor-promoting AR agonist in some men, and 2) have any of you guys discussed a 5ARI as a possible solution (to this possible downside of abi therapy) with your docs?
Me too in fact I will message the clinic.You guys are scaring me with this.
I was on Finasteride since day one (began 2 years ago) from the Urologists prescription. My refill status came up a week ago as "can not refill" rather than we will contact your dr.
My guess was since I started Abi about 5 months ago dr. determined Finasteride (or insurance determined?) wasn't necessary.
I was ok with dropping the Finasteride if it isn't doing anything. Heck maybe my eyebrows and goatee will get back to normal ha.
I have enjoyed my wifes joy at the fuzzy growth on my bald spot though.
What a life. I remember way back in the 90's when ads for Finasteride came out for hair loss. I looked into and thought shit that stuff messes with your hormones there is no way I am going to take that.
Now I am Mr. Lupron, chemo, abi, and Finasteride himself.
I wouldn't be too scared... abi is proven HIGHLY effective, without a 5ARI. Maybe look at the 5ARI addition just as a potential (and still unproven) bonus, for SOME men.
Personally, I am FAR more interested in the potential for doing abi in on/off cycles to delay resistance. (See LearnAll's post above on Moffit Center Researchers.)
"This treatment may result in development of non-alcoholic fatty liver diseases (NAFLD), insulin resistance (IR), type 2 diabetes (T2DM), dry eye disease, potential kidney dysfunction, among other metabolic dysfunctions."
That is not an answer to your question, but there is also different percentage of side effects to consider between these two drugs for anyone who plans on starting on them. Real world comparison of finasteride and dutasteride urologytimes.com/view/real-...
Great discussion, cycling seems to be a recurring theme.
I was on Finasteride for six months before being diagnosed with PCa. Urologist immediately took me off Fin because he said it can exacerbate the cancer. Is that not so?
Sorry to say that your Uro does not know much about 5ARI meds such as Finasteride ,Dutasteride etc. These drugs block conversion of T into DHT. DHT is most potent form of T.The 5ARI drugs block the enzyme which is required for converting T into DHT. This results in very low levels of DHT. And that results in slowing of growth of cancer cells.
Not so. He is probably conflating studies for finasteride for possibly preventing PC. Not applicable to those who already have PC. Another reason to have an MO in the driver’s seat. (Though there are some notable exceptions of very sharp urologists.)
So far as I know, the only reported downside to finasteride (as it relates to PC progression) is that it can "mask" what are considered "true" PSA readings... and make them appear lower than they would otherwise be, but possibly without any actual regression of the PC.
I’ve been using dutasteride, Lupron and Xtandi for over 7 years now, originally prescribed by Snuffy Myers. As Nal said, the goal being to prevent T from being converted to DHT. None of my current docs including Sartor, have expressed any issue with continuing to take it.
Great thread! I was on Avodart for ten years to avoid surgery or radiation . I also took that drug that women take which lowers estrogen ( since when Avodart blocks T >DHT in the capsule it aromatizes into estrogen . Avodart cut my PSA in half from 8 to 4 in 2009. I stopped Avodart for one month in 2019 and my PSA went to 12. Return to Avodart no longer lowered PSA . I finally started Orgovyx and Zytiga with pred 3 months ago (PSA61) and am getting 26 radiation treatments currently .
If the abiraterone metabolite of concern becomes a significant promoter then you would expect to see a rise in PSA that would then drop if abiraterone was discontinued. Would it not? That would be analogous to the situation with bicalutamide when it starts to promote PC growth in certain individuals. I am just speculating here.As for dutasteride while cycling high T (mBAT), I have thought about it. But when on SPT it seems like stepping on the gas and the brakes at the same time. (?) Perhaps could be of some utility during “off” cycles if not using some form of ADT to get fully castrate? I am adding Firmagon 80 mg at the start of my one month off cycles because my T has not been dropping sufficiently (even though PSA has remained very low).
Hello Noahware, I have been taking daily 0.5 mg dutasteride since I started abiraterone in August 2020. The rationale is to inhibit the formation of abiraterone metabolites that are AR agonists. I have not had any side effects or liver issues. I should mention that I have reduced my dosage of abiraterone from 1000 mg/day to 250 mg/day with food. I am not sure that it has delayed progression, but many of us hedge our bets. Cheers, Phil
I plan to add the dutasteride and reduce dosage, as well, pending an upcoming discussion with my MO. I only just read about the potential "to inhibit the formation of abiraterone metabolites that are AR agonists." Certainly did not hear about it from my doc... did your doc tell you about that, or other way around?
Hello Noahware, I requested it from my MO. I explained why but he wasn’t happy. After persisting he finally agreed and said it wasn’t any skin off his nose which was a kind of a strange reply. Cheers, Phil
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Taking Xytiga (Abiraterone) with food.
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