General question

[Chris52981]

What exactly does a second line hormone do when you are hormone sensitive? Like Zytiga added with lupron-

[GP24]

It reduces the testosterone level even further than Lupron will. The lower level is more effective against aggressive cancer e.g. with bone mets.

[Chris52981 in reply to GP24]

Is it better than lupron alone for hormone sensitive metastic PC

[GP24 in reply to Chris52981]

Studies showed that it is better if you have bone mets. However, if you do not have these, you can save yourself the side effects of Abiraterone.

thelancet.com/article/S1470...

[Tall_Allen]

Use of second-line hormone therapy in newly-diagnosed metastatic men delays the time to castration resistance and improves survival markedly.

While Lupron only prevents the testes from manufacturing testosterone, Zytiga prevents the adrenal glands and the cancer itself from manufacturing other androgens too. Powerful antiandrogens, like Xtandi, block the cancer from using any androgens and prevents the androgen receptor on cancer cells from translocating to the cell nucleus where it is activated without external androgens. (They replace Casodex, a very weak, much less effective anti-androgen). When most prostate cancer cells are so completely deprived of androgens, they die off.

[Chris52981 in reply to Tall_Allen]

Now if that stops working would that make you castrate resistant - is Zytiga used for that as well

[Tall_Allen in reply to Chris52981]

Castration-resistant means that PSA or metastases increase in spite of Lupron (or similar). Lupron doesn't really "stop working" - it still helps by reducing testosterone. Zytiga (or Xtandi) is indicated for both metastatic hormone-sensitive and metastatic castration-resistant.

[Chris52981 in reply to Tall_Allen]

HowWould you know when Zytiga loses its effects - if he is hormone sensitive

[Tall_Allen in reply to Chris52981]

PSA or metastases will increase as the cancer becomes Zytiga-resistant.

[Chris52981 in reply to Tall_Allen]

Thank you -so when or if Zytiga stops working there are other things that can -

[Tall_Allen in reply to Chris52981]

There is a lot of cross-resistance between Zytiga and Xtandi - Xtandi might still work, but probably not for long. Cross resistance with the newer hormonals (Erleada and Nubeqa) is unknown, but probably occurs. Chemo and other substances may reverse hormonal resistance. We saw yesterday that even though BAT may reverse Zytiga resistance for a time, there was no net survival benefit.

[Chris52981 in reply to Tall_Allen]

So it’s possible Zytiga could work for some time

[dockam in reply to Tall_Allen]

Okay, that explains my PSA rise over 2 month whilst on Xtandi and only on Abiraterone from 01/2020. Next up is a rechallenge with Taxotere, sent the Kaiser MO what I read and she agreed to do that.

Then the PCa may then become resensitized to Abiraterone or Zytiga.

Hope springs eternal

“Hope springs eternal in the human breast;

Man never Is, but always To be blest.

The soul, uneasy, and confin'd from home,

Rests and expatiates in a life to come.”

― Alexander Pope, An Essay on Man

Mahalo

Fight on Randy

[Chris52981 in reply to dockam]

clinical reoccurrence metastic prostate cancer - is Zytiga lupron prednisone and Xegeva a good combination or a SOC for hormone sensitive

[dhccpa in reply to Tall_Allen]

Why does that combo eventually fail as well? How much average lifespan does adding Zytiga or Xtandi on top of Lupron early add?

[Tall_Allen in reply to dhccpa]

Because the cancer mutates rapidly, it will eventually attain a genomic signature that is resistant to whatever you throw at it. Using Zytiga or Xtandi when newly diagnosed adds about ⅓ to survival.

[Break60 in reply to Tall_Allen]

TA

You use the term “ newly diagnosed “ with regard to the effectiveness of second- line HT. Does that mean that these tx don’t work for recurrent pca?

Also, I switched to estradiol patches from Trelstar nearly two years ago and have had undetectable psa and been castrate sensitive since. If/ when estradiol stops working, would second- line HT work?

Bob

[Tall_Allen in reply to Break60]

We have statistically reliable data for newly diagnosed metastatic men, or for all men with metastases, but no statistically reliable data for the subgroup of recurrent men with metastases. There are clinical trials that will someday prove or disprove their value for recurrent men with metastases .

I have no idea if those medicines will work after estradiol.

[Break60 in reply to Tall_Allen]

Thanks

[Chris52981 in reply to Break60]

My dad is recurrent as well and now he is back on stuff since his reoccurrence and scans saw a few Mets - he is on Zytiga, back on lupron, prednisone and xgeva - first time today

At first 5 years ago he had stage 3 b fast forward through radiation and lupron then on vacation because PSa was undectable untill this year- in august had Axumin scan -mRi on lumbar and thoracic spine- and started seeing medical Oncology and the new

Regiment. He sought a second opinion 5 years ago with Fox chase and those drs chose the drs he will be working with at our local hospital.

[Knittingque in reply to Break60]

I know this is 3 years since you posted and l hope my reply finds you well. I noticed you are using E2 patch. I am having an orchiectomy to get off the dreaded chemical casraton route which has been now since 2013. My Psa went upto 82 1 yr ago, new label NMCR so they added Xtandi in November which has brought psa to 12.0 so its working wel, T level is 00.02 (zilch) and fatigue is very hard, l have requested E2 patches for after surgery, would you say that the added E2 patch gave you some energy as well as conserving bone health. Thanks for your time, Brian

[Break60 in reply to Knittingque]

Yes I def felt better when I got off LHRH and on the patches. My problem over the last few years has been incontinence, not Pca. It’s so bad I’m afraid to do heavy exercise like I used to. I’ve tried the sling and AUS. I’ve been using Foley catheter since March 2023.

[Knittingque in reply to Break60]

Thanks for your reply l am hoping for some energy and well being once l add the E2 probably have to play around with it to find the right dosage, Gp said start on 0.25mcg, what is your dosage incidentally.l am sorry you are still having challenges with the incontinence,

[Break60 in reply to Knittingque]

I’m using three .1mg patches changed weekly.

[tango65]

Abiraterone blocks the production of testosterone everywhere in the body, including the adrenal glands which are not inhibited by Lupron or similar drugs. Besides this action abiraterone blocks the production of testosterone inside the cancer cells and it can connect with the androgen receptor resulting in his inactivation.

erc.bioscientifica.com/view....