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Re: Why does Zytiga fail?

>> I can't find any web source that explains this.


Hi OC,

If you go to the site below you will see several references to research that has identified particular genes and proteins which, it is thought, when mutated, cause an increase in the number of receptors, resulting in the ability of a smaller amount of testosterone to have a field day.

http://www.sciencedaily.com/releases/2014/02/140210161234.htm
OC in England[/quote]

Re: Why does Zytiga fail?

Thanks for that, Jack, I read it but it went largely over my addled head. SPOP Mutations eh? The answer may lie in some future research on these proteins. Personally, Zytiga, thankfully is still driving my PSA down, albeit at a slower pace now I'm into my fourth month on the stuff. PSA just 1.6, but I'm alive to the possibility of future failure.

OC in England

Re: Why does Zytiga fail?

To jump in here rather late - Zytiga fails sort of for the same reason every treatment eventually fails. In the millions and millions of cancer cells there are pre-existing 1 in a million mutant cells that have some ability to grow in the presence of the drug. The resistant cells multiply and eventually take over the population. When that happens the treatment no longer works. As mentioned, this can be overproducing the androgen receptor by having multiple copies of the androgen receptor gene. This is a signal amplification strategy. But you could imagine a mutated androgen receptor that was permanently stuck in the activated mode or mutating some other receptor to activate the androgen response regions on the DNA etc. The big problem is that as the cancer progresses the individual cells manage to jettison the error-checking systems that are designed to prevent the survival of mutated cells.

The reason that some people fail sooner than others is related to the nature of the specific cell that had the mutation that conferred drug resistance. It might be a fast grower or a slow grower. It might grow very slowly until a different mutation shows up in one of its descendants that can grow faster. Its Darwinian evolution.

Re: Why does Zytiga fail?

Old Codger,

I believe a better answer is: There is no way to determine, before hand, how long you will respond to Zytiga. I believe your prostate cancers androgens receptors mutate to become more androgen independent and can survive in very low levels of androgens. I believe the time it takes for this to happen varies between patients and is probably associated with the genetics of your particular cancer.

Regarding treatment options after failing Zytiga, there are more targeted therapies like radium 223, secondary hormone drugs, and chemo.

Fred

Re: Why does Zytiga fail?

Fred, Thanks for those thoughts. They match my own feelings. However, nobody on this forum or so far as I can tell on the wider web, has yet said why Zytiga fails, ie, following some research with proof supplied. For those who experience failure of this drug, or others which may follow that failure, it seems that the Oncologists follow their feelings, too. In other words, the process is a hit and miss one - keep trying until something works. Not very scientific, is it?

Re: Why does Zytiga fail?

Old Codger,

I agree. I have been pretty healthy all my life until I got this disease. The more I did my research the more I said where is science in medicine. We had a urologist come to our support group meeting and I had the results of 200 patients using ADT3 as primary treatment. She looked at my abstracts and said that ADT3 was not a treatment for PC. That seemed kind of strange to me since if their surgery fails, they hand you off to an oncologist that gives you hormone therapy.

Fred

Re: Why does Zytiga fail?

Boys,

I'm surprised that you seem to be still looking for certainty when there is none.

I realised a long time ago that much of the treatment offered to us PCa men is based on what I have referred to as "Medical Beliefs" rather than sound science. Indeed science which challenges the status quo is often ignored because it clashes with these beliefs. In days when I was more active on the web I would challenge doctors who posted "this is the way" to share with us the studies that supported their views, since they demanded that from us when we put forward alternative views. They could not - because often there were no such studies.

I've just had a series of discussions with my oncologist concerning my next step, given that the current combination of Androcur and Lupron seems to have failed. He suggested Zytiga (Abiraterone) despite the fact that it has only been approved for men who have failed chemotherapy, which is not the case for me. Although Zytiga is on the Pharmaceutical Benefits Scheme for men with failed chemo and would therefore cost me $5.60 a month if that was my case, since it is not it would cost $4,000 a month.

I suggested again that I should try diethylstilboestrol (DES) but he, as all doctors will objected on the grounds that it was a very dangerous medication with a high risk of heart failure. I tried to point out that applied to 5mg doses not the 1 mg dose I wanted. He finally agreed, very reluctantly on the basis “Well, it’s your life.” I have sent him this study 2003 DES Study and hope it will help him understand that there is good scientific evidence to support my case. I started DES yesterday.

Re: Why does Zytiga fail?

Terry,

I pretty much agree with all that you say. Just an update. The FDA, in December 2012, approved Zytiga for the use in metastatic castrate resistant cancer before chemo.

Fred

Re: Why does Zytiga fail?

And in the UK Zytiga is in use for non-metastatic PCa where ADT has failed, apparently approved by NICE and I think OK'd by the European Regulator too. Oz needs to catch up!

You're quite right to chastise me about seeking certainty but I was trained as a Physicist/Mathematician and old habits die hard and I do think Oncologists should know why a treatment fails so that they can sensibly prescribe something else. Good Luck with DES - my oncologist poo-poo'd this when I raised it as a possibility some months back!

OC in England

Re: Why does Zytiga fail?

Terry,

I hope you have good results with your new therapy. I do have questions, just out curiosity, about your stent situation, but I don't want to burden you.

Jack from Jersey

Re: Why does Zytiga fail?

Fire away Jack - I assume you've read the updates regarding the stents on my story at Terry Herbert?

All the best
Terry in Australia

Re: Why does Zytiga fail?

Hi Terry,

Were you sedated for the cystoscopy when the stent was put in and then removed? My urologist used the cystoscope just to take a quick around in the bladder. He used what I suppose was lidocaine and it turned out to be the most painful procedure I have experienced which lasted fortunately for only two minutes.

G'day

Re: Why does Zytiga fail?

I had a full anaesthetic Jack. The first procedure took over and hour and the second about forty minutes. I don't think the placement and replacement of stents could have been dealt with in any other way. The cystoscopy was incidental to the main procedure.

All the best

Terry

Re: Why does Zytiga fail?

Terry,

I appreciate the non-judgmental tone of your response. I couldn't fault you for thinking:

I don't think the placement and replacement of stents could have been dealt with in any other way, you idiot.

Jack from Jersey

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