Xtandi (enzalutamide) alone is superior to ADT alone at preventing metastases in "high-risk" recurrent men

[Tall_Allen]

"High-Risk"recurrence was defined as men who have had primary therapy (prostatectomy or radiation) but have had rising PSA but no detectable (on bone scan/CT) metastases yet and T≥150 ng/dl, and:

• PSA doubling time ≤ 9 months, or

• PSA≥ 1 ng/ml post-prostatectomy, or

• PSA≥ nadir+2 ng/ml post-primary RT

Xtandi+ADT performed significantly better than ADT alone (+ placebo). Xtandi monotherapy performed significantly better than ADT alone. No comparison yet on Xtandi monotherapy vs Xtandi+ADT. Also improved time to PSA progression/castration-resistance and time to chemo. No data yet on overall survival.

Men achieving PSA≤ 0.2 ng/ml were given a vacation from therapy until PSA rose again. No QOL data yet.

pfizer.com/news/press-relea...

[treedown]

Is anybody thinking that the Xtandi monotherapy might be equal to as a effective as Xtandi+ADT?

[Tall_Allen in reply to treedown]

It was randomized, so we shall see. If so, and if the QOL (other than gynecomastia) is better with Xtandi monotherapy it will be good to know.

[treedown in reply to Tall_Allen]

Is Xtandi more likley to cause gynecomastia than say Zytiga or ADT alone that you know of?

[Tall_Allen in reply to treedown]

Yes. Xtandi is a powerful anti-androgen=it blocks activation of the androgen receptors on all cells. When that happens, testosterone, having nowhere to go, accumulates.The excess testosterone gets metabolized into estrogen and DHT. It is the excess estrogen that causes gynecomastia. Tamoxifen blocks estrogen in breast tissue.

[StayingOptimistic in reply to Tall_Allen]

TA, I am very close to the idea of starting ADT again( Firmagon). Does that mean I can ONLY start xtanti without starting Firmagon?

[Tall_Allen in reply to StayingOptimistic]

If the choice is only Firmagon, Xtandi monotherapy performed significantly better than it.

[StayingOptimistic in reply to Tall_Allen]

will Xtanti be able to kill resistance cells and sensitive ones?

[Tall_Allen in reply to StayingOptimistic]

This trial was for recurrent men who were all still hormone sensitive. But Xtandi+ADT is also indicated for castration-resistant PCa.

[cesces]

I have always thought of Xtandi as being part of androgen deprivation therapy.

Can someone explain what exactly constitutes ADT?

[Vynbal in reply to cesces]

There are 3 classes of drugs that used to fight PCa based on the fact that PCa cells will not replicate without being activated by testosterone. Since most T is made in the testes, the first group works by blocking the signal from the pituitary to the testes to make T. This group includes Lupron, Firmagon, Orgovyx, and other GnRH agonists and antagonists.

A small amount of T is also made in the adrenal glands. The second group (zytiga) disrupts the formation of a precursor molecule thus preventing the additional T.

The third class is anti-androgens which block the androgen receptors (in all cells), thus preventing whatever T that remains from being used. This class includes the -lutamide family of drugs.

All of these drugs deprive PCa cells of the Androgen needed to replicate, and so yes, they are all Androgen Deprivation Therapy. However, in the context of TA's post, only the first group is included in the term ADT.

[Spring15-3]

Husband's psa stayed super low on this but be careful with it. Within months he was acting like he had alzheimers and was sleeping 15+ hours a day. None of the docs told us it crosses the blood brain barrier and that this can be a side effect. We finally got him changed over and it's not great (the lupron) he can at least function now

[MProust in reply to Spring15-3]

---Thanks for the information. Is he on Lupron only? What have been his side effects with the Lupron?

[Spring15-3 in reply to MProust]

it was the xtandi that was really bad. He's on lupron and nubeqa now. He still has brain fog and he stays tired but not like with the xtandi

[alephnull in reply to Spring15-3]

I am really late to the game here, haven't been on the site in months.

But, when it comes to brain fog, I had a MAJOR case of it. I am a computer programmer, the fog almost cost me my job.

But, my PCP put me on Adderall, it has been a God send. My mind is clearer than it has been in 10 years (how long I've been on ADT), the last year with Xtandi.

I cannot believe the difference.

[Spring15-3 in reply to alephnull]

I wish. Husband has ADHD which is gun since we've added brain fog to it. Nobody wants to prescribe Adderall since he's 81 and genetic testing done by the VA shows Strattera would be problematic