Zytigia mechanism of effectivity

[Proflac]

Hi. Sorry for what might seem a dumb question.Can someone help with a query about the mechanism of effectivity of zytigia. Is it effective (for some) because it keeps T low or is there some other action? If ADT e.g lupron etc is keeping T low and PSA stable what is the added benefit of abiraterone? Is the objective of tx to keep T low, get T lower or is there something else which abi can do to help stop grow/spread. ? Thanks.

Ps.Merry Xmas to all. Xx

[noahware]

I think Abi (Zytiga) keeps T lower than standard ADT alone because it acts on an enzyme needed for T production. So it limits androgens produced by the adrenals, as well as androgens produced by the cancer cells withing the tumor itself.

Perhaps someone can answer this second related question: if this drug is so good at limiting T, why are the standard ADT drugs even needed? What would be the possible medical disadvantage of Zytiga monotherapy, as opposed to combining it with Lupron, Firmagon, etc.?

[pjoshea13]

Classic ADT inhibits gonad production of androgen whereas Zytiga inhibits all production (gonad, adrenal & PCa cell). So why continue with basic ADT?

Here is my answer from 3 years ago:

"The rationale ..... is given in the SPARE paper [1]:

"The value of continuation of luteinizing hormone-releasing hormone (LHRH) therapy in castration-resistant prostate cancer (CRPC) remains controversial and clear evidence is lacking. Argumentation for cessation of LHRH therapy is the prolonged suppression of testosterone levels after the withdrawal of LHRH analogues and the fact that disease progression occurs despite castration levels of testosterone. Especially upon treatment with the life-prolonging cytochrome P450 17-alpha-hydroxylase (Cyp17)-inhibitor, abiraterone, which has the ability to further suppress testosterone serum levels over LHRH therapy alone, continuation of LHRH therapy seems to be negligible. However, the proven increase of luteinizing hormone levels after LHRH withdrawal, which is even further increased by abiraterone, may counteract the effects of abiraterone by the induction of enzymes of steroidogenesis. Therefore, cessation of LHRH therapy when starting treatment with abiraterone in CRPC may display an unpredictable hazard to the patients. This study will explore the role of continuation of LHRH therapy when starting treatment with abiraterone in patients with asymptomatic or mildly symptomatic, chemotherapy-naïve CPRC."

-Patrick

[1] ncbi.nlm.nih.gov/pmc/articl..."

[tango65]

You will live longer. It decreases testosterone from the adrenals but it also affects the intracellular production of testosterone by the cancer cells.

[Proflac in reply to tango65]

Thanks.

[Tall_Allen]

Unfortunately, NICE (England) doesn't approve abiraterone for hormone sensitive metastatic patients. It is a mistake. A major clinical trial also found that it improves survival even in very high risk patients who do not yet have any detectable metastases.

Abiraterone prevents the adrenals from manufacturing testosterone and similar androgens that can activate the androgen receptors on your prostate cancer cells. When they are activated, the cancer cells can replicate. It also prevents the cancer cells from making their own androgens, which they would otherwise do.

Lupron only prevents your testes from manufacturing testosterone. Testosterone is one of several androgens that can activate your androgen receptors. You have to get rid of ALL sources of ANDROGENS.

It also delays castration resistance vs Lupron alone.

[jfoesq in reply to Tall_Allen]

Tall-AllenAre any studies taking place comparing Abi+Lupron versus just Abi ? Have they be done already?

Thx!

[Tall_Allen in reply to jfoesq]

There was a small randomized trial in mCRPC patients. The two didn't have significantly different results (radiographic progression or time to PSA progression) at one year, but they would have to do a bigger trial with longer follow-up:

urotoday.com/conference-hig...

[Poowater in reply to Tall_Allen]

A great reply.

[Proflac in reply to Tall_Allen]

Thanks for the explanation. As I am sure you know, NICE did allow it last year in lockdown as an alternative to chemo for those who were still hormone sensitive metastatic and haven't taken it away from those people - but not sure what the situation would be now for someone newly diagnosed with that stage. My husband was prescribed abi in the covid context so never did have chemo. No one has suggested having chemo now that its being done again - but I am not sure why? Would there by any benefit from this? Or is abi going to always be the better alternative to chemo, instead of alongside or after chemo?

[Tall_Allen in reply to Proflac]

Not sure that it's better, but it's at least as good.

ncbi.nlm.nih.gov/labs/pmc/a...

There is evidence that doing them at the same time increases survival, but if they were not started at the same time there is no benefit in starting one until the other fails.

[Poowater]

It's a second generation therapy stopping testosterone production in the adrenal gland. You should also be on Lupton or some other ADT.

[Poowater in reply to Poowater]

Sorry Lupron. With the addition of Zytiga your T should be stopped completely.

[Proflac in reply to Poowater]

thanks, but what is completely? My husbands T is 5 - I think thats n/mol

[j-o-h-n]

There's nothing stupid about a question......... it sometimes is the answer(s)....

Good Luck, Good Health and Good Humor.

j-o-h-n Saturday 12/25/2021 7:28 PM EST - Happy Christ's Birthday.