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Advanced Prostate Cancer
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Enzalutamide resistance. What's next?

My dad (72) has Gleason 9 stage 4 Prostate cancer. He has been through all the standard hormone therapy, doxetaxel and is now on enzalutamide but is showing some resistance to it. The last three PSA tests have shown a rise. What options do we have next? We are in the UK. I am feeling very upset about this drug no longer working effectively and am hoping that there are some success stories with either resensitising to enzalutamide or more drugs. The oncologist said that Bipolar Androgen Therapy would not work given that hormone therapy has already failed... and that aptalutamide wouldn't work for long given that it uses the same mechanisms as enzalutamide. He did however say that there are new agents. There are some very clever people on this forum so I am hoping you can help me with this.

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The new agent you need is darolutamide

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Thanks gusgold. Do you know how long it is expected to work for? Also, can anyone unveil any magic ways to extend enzalutamide. Does Quercetin actually work?

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My guess would be 24 months...need to get in clinical trial....good chance low dose DES 1mg would work

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Is Darolutamide approved in the UK?

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I would suggest genetic testing to see if there are any gene mutations that would allow for targeted treatments. If you can see how the cancer had evolved under treatment, you can possibly direct the treatment in a more effective way.

Also, see if you can find clinical trials in your area.

Here's a link to one site for UK clinical trials. I'm sure there are others. ukctg.nihr.ac.uk

Good luck with treatment and let us know what you are doing.

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Thanks gregg57. My problem is that my dad is committed to following the path that his oncologist sets. His oncologist is Dr Vincent Khoo at the Royal Marsden. And who am I to argue. I know nothing and this man has dedicated his life to research. How can I purport to know what's better for my dad and advocate for him?

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I would suggest researching the advice you received here. You can print it out and present it to the doctor. You can have a discussion about everything with your doctor. But at the end of that, your dad makes the decision, not the doctor. You are never committed to the path that your doctor wants to take. If you don't agree with the doctor, find another.

I know I'm being blunt here, but you did say you wanted to advocate for him. I think you are doing the right thing by researching the options for him.

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Hi

I am in the UK and started BAT two weeks ago to hopefully get HT working again. I found It quite difficult to get my oncologist to agree

Let me know if you want any information

Si

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gregg57--gave best answer---but you may need to be gene mapped first, And I do not personally agree that BAT would be dead--You need to talk to Dr. Demeade's Group at John Hopkins--they will have the definitive best and last answer to BAT.

Nalakrats

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Also when Xtandi stops working it is many times related to the AR-V7 Gene Splice Variant being turned on--it has been shown that High T Therapy can turn the Gene Splice off--allowing Xtandi to work again---this according to my Geneticist>

Nalakrats

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Did he fail docetaxel, or just stop it? Sometimes taxane treatment or retreatment (Taxotere or Jevtana) can restore sensitivity to Xtandi or Zytiga. BAT should only be used in asymptomatic or minimally symptomatic men - otherwise it could kill him faster and very painfully. But it can be tried in men who are castration resistant:

pcnrv.blogspot.com/2016/09/...

Transdermal estrogen, which his doctor can prescribe, sometimes works when all else fails. If nothing else, it should mitigate hot flushes. It should be taken with 10 mg tamoxifen to prevent breast effects.

There are several hormonal agents (e.g., apalutamide, darolutamide, VT-464, etc.) that are only available in clinical trials. I don't know if Provenge is approved in the UK, but there are several immunotherapies in clinical trials. If he has bone mets, Xofigo may be worth a try. There are other radiological agents they are trying in Germany.

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You've gotten great advice from excellent advisers. God bless you for being your Dad's advocate.

Good Luck and Good Health.

j-o-h-n Friday 03/30/2018 1:27 PM EDT

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There are multiple "modalities". Surgery and hormone therapy are the well established standards. Chemo has proven effective now with docetaxel and later jevtana.

It is false that "apalutimide will fail because abiraterone has failed". So there are homone related things left to be done, as well as chemo things.

There are other targets. PSMA has been a diagnostic target and is is being trialed as a theraputic target, with radioactive drugs. These are successors to 223Radium that was used for bone mets. They are 177Lu and 225Ac, but these are not self-guiding like the 223 Radium is, and so they are joined to a PSMA antibody, or to just the ligand arm of the antibody, or to an even smaller patch of protein (styled as a "small molecule" conjugate).

External radiation you know of, and are one way of directing high energy at a tumor.

If you can get someone to look at the clinical trials gov site for you , you can see how much work is being done for people just like your dad.

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