Zytiga

[PCaWarrior]

Zytiga (Abiraterone Acetate)

o Zytiga (abiraterone acetate) is an androgen biosynthesis inhibitor used in advanced prostate cancer to further suppress testosterone production beyond standard androgen deprivation therapy (ADT). It is typically used with prednisone to manage side effects.

o Blocks Androgen Production at Multiple Sources

1. Standard ADT (e.g., Lupron, Orgovyx) suppresses testicular testosterone production by inhibiting the hypothalamic-pituitary-gonadal (HPG) axis.

2. Zytiga goes further by blocking CYP17, an enzyme involved in androgen synthesis in the adrenal glands and prostate tumors.

3. This reduces residual androgens, which can still fuel prostate cancer even with ADT.

4. After discontinuing Zytiga it can take around a month for the enzymes to recover.

o Prevents the Synthesis of Key Androgens

1. CYP17 inhibition blocks the conversion of pregnenolone and progesterone into androgens like DHEA, androstenedione, and testosterone.

2. This starves prostate cancer cells of all possible androgen sources.

In 2019 I used tE2 for ADT and Zytiga to mop up any remaining biosynthesis. T held undetectable and so did PSA.

I'm thinking of adding it to pBAT. Thoughts?

[Shellhale]

Does Zytiga allow testosterone to circulate in the blood similar to Nubeqa and Xtandi? I've been thinking about this also since husband's PSA is rising on Nubeqa. But don't really like the idea of taking it with a steroid. Maybe forgo the prednisone. But I don't know enough about it. A good discussion point with the MO at next appointment

[PCaWarrior in reply to Shellhale]

No it doesn't. Zytiga stops biosynthesis of androgens.

The anabolic blunting of Zytiga is very similar to the blunting via Nubeqa or Xtandi. I prefer Zytiga and Nubeqa more than Xtandi. Xtandi was terrible for me.

The steroid is a corticosteroid. It does two things. Bottom line is that it's not an anabolic steroid. It ends up replacing cortisol.

Talk to your MO. They should be able to explain it to you.

Technical junk:

Zytiga is designed to inhibit CYP17A1, an enzyme critical to androgen biosynthesis. By blocking CYP17A1, it reduces the production of androgens from the testes, adrenal glands, and even from within the tumor microenvironment, which is particularly important in castration-resistant prostate cancer.

The CYP17A1 enzyme is necessary for synthesizing cortisol (and androgens). The reduction in cortisol leads to a compensatory increase in ACTH (adrenocorticotropic hormone), which then stimulates the adrenal glands to produce more mineralocorticoids. This increase in mineralocorticoids can cause side effects like fluid retention, high blood pressure, and low potassium levels. Prednisone is prescribed to replace the reduced cortisol and suppress ACTH production, thereby mitigating these mineralocorticoid-related side effects.

I used Zytiga with tE2. I was pleased with the combination. I wasn't pleased with the gyno, muscle wasting and libido loss.

[Shellhale in reply to PCaWarrior]

Okay makes more sense now. I understand why predisone is needed. So was your testosterone at castrate levels while on Zytiga? That is why he can't tolerate ADT the lack of no testosterone effected him mentally really bad. The muscle wasting and libido loss he won't like either.

[PCaWarrior in reply to Shellhale]

My testosterone was undetectable. I was using estrogen patches for ADT so my mental status was ok (not great), but muscle wasting, libido, and gyno made me stop after 4 1/2 months.

I can't recommend any of what I did - worked for me but will it work for you? It isn't SOC. I went for constant high testosterone. Did that for 2 years. Then BAT. I'm still doing BAT. It's been almost 4 years. Great muscle gains. Good libido. Bone growth. Joint health. In my case I have very good cancer control too.

[Shellhale in reply to PCaWarrior]

This is the route he perfers to go, keeping his testosterone. Your book is so well done and thought out. I plan on going through it all. It seems that you have a bio medical engineering background? We plan on getting more DNA and RNA sequencing and then coming up with a more long term control plan. I like that there is alot of options available just need to fine tune what works for individual biochemistry.

[PCaWarrior in reply to Shellhale]

Thanks for the compliment. I was an engineer for a medical company. So I had a little background in FDA, drugs, etc. But really what made me learn this stuff was that fact that I got cancer in 2018. Stats were grim. I was 55 and it didn't look good to get to 60. That'll get you studying.

Since you have my book have you looked at my backup plans? I stopped making them because there are just too many and pBAT has been working great for 4 years. I know a guy who has been using a modified version of pBAT for over 7 years. He's still HSPC (as am I). Another guy has been using a modified regular BAT program for 14 years! His PSA has crept up to 4 but the doubling time is long.

Remember, testosterone means nothing if the ARs aren't functional. If he uses an ARSI as monotherapy his testosterone will be high in his blood but almost all of it will be blocked from acting (Nubeqa is estimated to block 99.5% of DHT).

[Shellhale in reply to PCaWarrior]

It's interesting because he keeps getting more muscle gains. He lost 40 pounds in the beginning and has gained back 10 pounds in muscle mass. He has no side effects at all on Nubeqa. He does take Perfect Amino and creatine monohydrate on workout days. I tell him to take those amino supplements only when he is working out, so it's not utilized by PCa cells. I haven't looked at the back up plans yet. This is good to know that BAT has been so effective. I have read it works well with TP53. I believe you are alot smarter then this cancer. Always ahead of it. That's what is effective. Have you listened to Cancer Patient lab on Utube? youtu.be/4hiJE0A8XNM?si=ff4...(Not working as expected?) are segments in the video collections on high risk PCa that meet once a week and they have segments strictly on BAT where men share their experiences and personal combination of techniques that are used. What has worked and not worked. Alot of these men have medical backgrounds a few are doctors and several engineers. Thought I would mention it but you may already know about it. Thank you again for sharing all of your knowledge.

[PCaWarrior in reply to Shellhale]

Cancer Patient lab. I'm a member and led one of the BAT sessions. Other BAT presenters were Antonarakis and Sartor. I'm trying to get Denmeade or Sena to present.

Creatine monohydrate. Good. I've been taking it since 1994. The only sustained break I took was in 2024. Wasted year. It isn't therapeutic for PCa and it doesn't hasten progression. Appears particularly important during ADT or ARPIs.

[PCaWarrior in reply to Shellhale]

DNA testing? somatic and/or germline?

RNA testing seems promising. It isn't well controlled or understood yet. No harm in more data. A few of my friends relied on RNA testing, proteomics, etc. Unfortunately they are no longer with us. I don't know if I would let RNA testing outcomes guide my therapy decisions. DNA testing, in contrast, can be very actionable. Somatic in particular.

And you are aware of the possible changing results? Germline is a one and done thing. It should never change since it is inherited. Somatic covers active mutations. I get mine tested once or twice a year (Guardant 360 is the test I've been using).

[Shellhale in reply to PCaWarrior]

Yes I am only focused on somatic testing. Germline was done at dx and there was nothing there anyway. That is sad about your friends. I thought you may have known about that group. Lol

[PCaWarrior in reply to Shellhale]

I did germline at dx and nothing was there. But I redid it. Free and non-invasive. I don't know the reliability of the various tests but I figured, why not do a double-check and also provide some info for promise?

prostatecancerpromise.org/

Edit: I ran a query through an AI. I haven't checked but this is what it spat out: "...Overall, when a validated gene panel is used under quality-controlled conditions, germline testing in prostate cancer reliably detects clinically meaningful mutations, with accuracy generally exceeding 95% for established pathogenic variants."

Personally, I don't want to accept a 5% risk for my kids if I don't have to. "Assuming the two tests are independent and each has about 95% accuracy, the probability that both would miss a clinically meaningful mutation would be about 0.05 × 0.05 = 0.0025 (or 0.25%). That means the combined accuracy—i.e. the chance that at least one test detects the mutation—would be roughly 99.75%. However, note that in practice, if the tests share similar methodologies or systematic biases, the improvement might be somewhat less than this theoretical maximum."

[PCaWarrior in reply to Shellhale]

If you're interested in creatine, download my book again. I beefed up the creatine chapter last night.

[Shellhale]

I will download again. Thank you. He also did the promise genetic test. They found nothing as well. Only shows mutations with the tumor DNA unfortunately

[PCaWarrior in reply to Shellhale]

Do you have kids? I have two sons so I was overjoyed when my germline test came back clean.

[Shellhale]

Glad germline came back clean! Yes, I have 4 kids with my first husband who passed in 2006. My oldest son also passed in 2020, related to the fentanyl crisis we are facing. I've educated my 2 other sons and my daughter's husband about PSA testing. I worry about my son who is 26 and he is already hypogonadal and on Testosterone therapy that we arranged through the men's clinic. PCa runs in my family my uncle, grandpa and great grandpa all had PCa. My great grandpa died from untreated PCa at 99 years old. My other uncle had bladder cancer. My dad only has BPH and I believe he may have protected himself all these years being a type 1 diabetic. He has sense had a pancreas and kidney transplant 17 years ago and no longer has diabetes. I told him to keep taking the metformin as protection against PCa. My husband has no family history of PCa.

[PCaWarrior in reply to Shellhale]

Their risk is high. My older boy's grandfather on his mother's side died of PCa. So, his odds are around 50% depending on the study. I'm already talking to him about it. PSA testing. Free PSA. He's only 17 but I talk to him about serious stuff like anabolic steroids and drinking. There are dangerous ways to do both and better ways. One of the anabolic steroids acts as a weak DHT blocker. If he's going to take steroids, drink, have sex, whatever, he's likely going to do that no matter what I say. So I took the tact of being a friend who just wants to help.

[Shellhale]

My son's are very high risk. They have already started baseline PSA testing. Being a friend is a smart way to handle it. My kids aren't afraid to tell me anything. I do my best anyway to keep it that way. I also do sleep study analysis as a RRT. One of the questions that comes up during my male patient appointments is getting up to use the restroom during the night. I can't tell you how may times I've been asked what is a PSA? Men that are at least 50 don't know what a PSA is. I am a big patient advocate. I've done lots of education and will continue. It's unfortunate that's it's not part of as man's routine physical test. They only know about it if they have a family history. I sent my husband to my PCP and it was the first thing he tested him for before he even knew about his urinary symptoms. We need to do better and I am trying to change that.

[PCaWarrior in reply to Shellhale]

Our education sucks in this area. And after diagnosis it sucks. I had to find clinicaltrials.gov by trial and error. For the first year I thought anything on pubmed was approved by the government. RRT? Reg Resp Therapist?

[Shellhale in reply to PCaWarrior]

Yes Registered Respiratory therapist. I work in acute care in the hospital settings and I also do contract work with Veterans evaluation services. I am currently holding semi monthly clinics doing diagnostic testing for the PACT ACT.

I am also searching clinical trials just need more DNA sequencing for latest tumor burden. Wednesday is the PSMA scan. I will probably read results before MO.

[PCaWarrior in reply to Shellhale]

Good luck! If he has zero mets, that's best obvi. If he's 5 or less, MDT (SBRT). I have some ideas about how to get the most out of it.

[Shellhale in reply to PCaWarrior]

Okay I will definitely let you know what results are. Thank you so much.

[Ichthus316]

Great discussion, thanks PCaWarrior and Shellhale