Xtandi + Zytiga Fails To Deliver

Looks Like Myers was wrong about 2 better than 1 but I wonder if the combination would give a longer time to progression to mCRPC

Gus

urotoday.com/recent-abstrac...

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  • Gus wrote:

    "Looks Like Myers was wrong about 2 better than 1"

    Myers didn't actually say that. What he did say was that protocols that are effective in other cancers all involve multiple therapies. Perhaps three or more.

    When Xtandi after Zytiga showed disappointing results, & vice versa, there were experts on the sidelines saying that the results were not unexpected. The reason being the anticipated overlap in the reasons for drug resistance - because both drugs essentially have the same target.

    If one fails Lupron, one is categorized as being castrate resistant. But Xtandi & Zytiga are castration drugs too. One targets an alternative source of androgen, while the other blocks the androgen receptor directly. In the cited study, the men were already CRPC cases, which means that some might not have responded to the other drugs, or might have responded poorly.

    The Myers concept, which seems to be novel only in the PCa world, is to hit the cancer from several directions. PCa researchers seem mostly intent on shutting down any androgen escape pathway.

    Before CRPC, we had terms like 'androgen refractory'. It eventually came as a surprise that the AR continued to be a player in advanced PCa. Researcers who had been stymied suddenly realized that ADT was failing because the patient wasn't castrate enough.

    My feeling is: Enough with the castration!

    But if we are going to continue down that road, why do the trials never include a statin? & shouldn't Avodart be included too? & so on. Let's close all the barn doors we can.

    &, ideally, this should coincide with ADT initiation - not failure.

    -Patrick

  • Great answer Patrick, I often wonder if I should return to a statin. Strange as it may be I have been hammering on the AR with many different drugs for a long time. and switching did give response in most cases, though now I slowly climb the steps with times going down a flight.

  • Myers did say it...he was talking about blocking PCa drug resistance and said Xtandi for the AR receptor and Zytiga to block access to cholesterol

    Gus

  • Can you point me to a study on relation to cholesterol meaning help me understand scientifically with the castration. I did read about statins, but for some reason , my brain is iverliaded, and I only retained the bottom line. ty, as always for these informative posts

  • But Zytiga doesn't block cholesterol. It blocks pregnenolone & progesterone from converting to androgens. Was he suggesting that this takes cholesterol out of the picture in terms of steroidogenesis?

    Was this in a vblog post?

    As we discovered, resistance mechanisms were similar for both drugs. Which limits their value when used in sequence - or together.

    -Patrick

  • Yes close all the doors if doing ADT---Lupron, Casodex, Proscar, Avodart, and DIM

    What I call a quintuple blockade.

    Nalakrats

  • Also as to Statins--in my case--the harm is worse than any benefits. I am super sensitive---and the most I can tolerate is 10 mgs. of Simi. Anymore I cannot pick up my arms. I know 10 is not enough for Pca benefit--but I have 14 other Supplements going down my gullet each--day--not knocking Statins--My Doc. told me I should be on them for Pca--just will not be able to in my case.

    Nalakrats

  • Hi, Nakakrats. Would you share which supplements you are taking. I'm on Lupron now as I get ready for salvage radiation in a few weeks. I'm consuming lots of soy products and taking 5000 units of D3 daily now.

    Thanks

  • I have done parts under my screen name here--like General health, Bone health, supplements for working out, muscle maintenance, and Anti Cancer--we are all pretty ok with each other here--prefer not to cause controversy , as not all agree with my approach---so give me an e-mail, and I will respond off site, with 45 years worth of study, and use.

    Nalakrats

  • Jvaughan0@gmail.comThanks

  • The abstract omitted important information. The crucial point here is that the study participants's PCa had already activated pathways to work-around Xtandi so the addition of Zytiga was not helpful since its action is so similar to Xtandi. What the abstract omitted was what was the response to just the Zytiga and prednisone after the Xtandi.

  • Meyers is not always right. Ask my Doc. who had to fix up 3 of his failures--Just about killed these men.

    Xtandi and Zytiga, will not work if your AR-V7 gene splice is turned on to the positive mode. You get about 6 months of seemingly positive results, then you wake up one morning and your PSA is out of Control. If men's AR-V7 is in the negative mode, the Xtandi and Zytiga can work wonders. I was going to get the test for the Gene Splice above at John Hopkins, but my Geneticist, talked me out of it. She explained that the AR-V7, can turn on and off. She has seen the Gene Turn on after Chemo, and has seen it turn off after Chemo, certain chemicals from heavy dose supplements, and other drugs can make the Gene Flip Flop. The 1,000 dollar test's value at the time of the test will tell you at that time whether the 2 drugs will be beneficial, or not--positive --no good---negative--good.

    Nalakrats

  • Gus,

    The answer to your question is actually as simple as the question itself, we can not know because the study did not ask this question. All we do know from the study is that the combination of these drugs does not have a positive effect on progression free survival. It does not even tell us if there is a change in progression itself.

    Joel

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