GTX-758 -- have you heard of this?

Estrogen therapies go back to like 1940's-50's and still are used here and there, so if it is estrogen therapy it is not all brand new, might be tweaked somehow so as to hope for a patent. The original patent on DES ran out around 1980-81' the same year that Lupron was patented and brought onto the market. Now that DES is not patented it is actually a man made compounded drug to mimic the original ingredients that DES was. It is well known now (not in the past) that 1-mg useage is very safe and can be very effective in some cases (not all). Costs about nothing in comparison today, I got mine for $130 per year (lol) and it out performed my ADT3 ($13,000 a yr.) that I did back in 2002-2004, and no side effects and no hot flashes and sweats, even with residual Lupron still good in me back when I started this regime.

Journal article from Journal of Urology (no less) Nov. 2003, found it safe in 1-mg and even could work on hrpca after Lupron or casodex failed on patients). I have the website link if you are actually interested to read it all. I was failing on ADT3 in 2004 with rises, went to DES 1-mg psa declined and stabilized very well and actually got 8.5 yrs. of control, until just recently now. It buildes bone density as explained in the Journal article and can save memory loss (those are taken away with many other drugs).

Now others will say these classes of estrogen drugs will kill you and cause dvt's, is not the full story or complete truth. Some people have high risk for clottings, they can be screened, INR protime blood test will tell you what level of blood thinner may be neeeded for added safety, Journal article mentioned aspirin alone may be sufficient for 1-mg useage. In the old days they gave 5 mg (too much), no screenings, no blood thinners and a few patients did get clots or dvts'. What is not mentioned is that the rest of the patients got very good responses and control, even some cures were claimed (prior to Psa era of course).

Estrogen drug choices already known and used: DES, estradiol patches and now even gels (can be customed made doseages now too), emcyt (estramustine pills), there is another one I can't remember the name of. Now in case you didn't know Dr. Fred Lee (inventor of cryo freezing) had PCa 33 yrs. ago, and was found incureable within 2 nd year, he is still alive 33 yrs. later and working 1 day a week still, his drug used was emcyt and how did he know to choose such???? The results are astounding and noteworthy, I have the weblink to his story if you are curious. Also, Dr. Premoli in Argentina uses estradiol patches on alot of patients, with an excellent history on patients and no clots, he tried to have his results published in American Journals, they rejected his stuff. In other countries these drugs are not hidden from useage but even endorsed. Thought you might find this information of interest, if not maybe somebody will be curious. Also, they have more recently found that not only is there an alpha and beta estrogen receptor in us, there are 3 or more other estrogen junk pathways and they currently have no clue on exactly how and why all these totally work in the PCa area. Plenty of unknowns on the exact biology on PCa in general, it is evolving still.

Zufus,

THANK YOU!! I loved reading your post. And Marshall and I would love to get any links to other stories and info that you would care to share. I am trying to absorb as much knowledge about this as I can. I really appreciate this. And I will be sure to come back and post our experience in this study (if Marshall gets accepted....)

Marilyn

I was in the GTX clinical study...66% got GTX and the rest Lupron. They were testing GTX compared to Lupron and I was one of the ones who got Lupron.

They canceled the study 9 months in (was supposed to be a year) because of GTX causing blood clots.....may have been resoved since then...that was about a year ago.

I already have an update. Our oncologist, Dr. Flaig, called this evening to say that there's a chance Marshall won't qualify for the clinical study of GTX-758 because of his weight. He says that one of the requirements to be enrolled in this study is a body mass index of 35 or less and he looked at Marshall's records and said it was going to be very very close.

So I found a BMI calculator online and the way we figure it, Marshall's BMI right at this moment is 34.8. So we have determined that we are going to really watch our diets between now and March 1st to be sure that at least he will pass that hurdle. Dr. Flaig said that he thinks this drug is going to be the drug of the future in the fight against prostate cancer so we are very excited about it!

Stay tuned for more updates.

Marilyn

Marilyn, crossing fingers for you. I am going to ask our doctor today about this. Keep us posted!

nhwife -- I would love to hear what your doctor has to say about this. Our oncologist just exudes excitement over this treatment and you can't help but get excited when talking to him about it.

Marshall has been doing a fairly good job of controlling the pain in his leg, but this morning he woke up with excruciating back and chest pain, and he hasn't had chest or back pain for a very long time, so today is a DOWN day.

Zufus -- I love reading your messages. You have truly done a lot of research and I am trying to soak it all up. Thank you!

Marilyn

GTX-758 aka Capesaris works by turning on a certain estrogen receptor (Estrogen Receptor Alpha) in the brain. This activates LHRH (it acts as an LHRH agonist, like Lupron), which increases production of the sex steroids by the gonads. That surge in testosterone then causes the brain to shut down any further production of testosterone. LHRH antagonists like Firmagon accomplish the shutdown directly without the initial testosterone surge. The advantage of Capesaris over Lupron is that it doesn't deplete estrogen the way Lupron does, and doesn't cause as many estrogen-depletion side effects like hot flashes, bone loss, thrombophilia, hypercoagulation, or increasing fat mass. At least that was the hope. In Phase II trials there was an increase in clots necessitating a reduction in dose before trials were continued.

Estrogens (e.g., diethylstilbestrol) have long been used to shut down androgen production in this way, and have been made safer by patches which don't cause the kinds of clot-producing estrogen surges that pills or injections do.

However, estrogen is a two-edged sword with respect to prostate cancer. There are two estrogen receptors in prostate cancer cells - alpha and beta. The alpha receptors, when activated, cause increased proliferation of prostate cancer cells; but when the beta receptor (which is highly expressed in healthy prostate cells) is activated, it slows down the proliferation of prostate cancer cells. Clearly the effect of estrogen on the brain in shutting down testosterone production has a much bigger impact on slowing the cancer down than its effect in directly stimulating the cancer, otherwise estrogen would never have worked. However, as time goes on, the cancer expresses more alpha receptors and fewer beta receptors, so I would expect its cancer-stimulating effect to increase. If I am right, I would expect Capesaris to become less effective over time -- we'll only know from the findings of these clinical trials.

Because estrogens act as both agonists and antagonists of the cancer, scientists have tried to develop kinds that only activate the beta receptor without activating the alpha receptor. These are called Selective Estrogen Receptor Modulators or SERMs. One such SERM called Clomiphene blocks the alpha receptor, and it would be counterproductive to take it with Capesaris. Soy isoflavones stimulate the beta receptor. Gamma and delta-tocotrienols are thought to enhance beta receptor activity too. It is available as a pure annatto extract from health food stores and on the internet. It’s important not to try to obtain it from other mixed Vitamin E extracts – even small amounts of alpha-tocopherol seem to suppress absorption of tocotrienols. This may be why Vitamin E supplements increased the incidence of prostate cancer in the SELECT trial. You might want to discuss with your doctor taking soy isoflavones and pure tocotrienols with Capesaris therapy if it doesn't violate the trial protocols.

- Allen

Here's a few more links for your reference...


prostatecancerinfolink.net/?s=gtx

tony

Allen- are you in the medical field, you have alot of info and input on PCa and drugs. As to responses on drug therapies for hrpca or those failing cure, seems no drug is curative but their seems to be some atleast anectdotal evidence of switching drugs to try and fool the cancer (per se) has some merit. Friend of mine has a unique story and evidence of controlling his PCa thus far and you would appreciate the concept on how and why it is currently working for him. He failed Lupron and other drugs, failed surgery early on 2004 and failed SRT, psa was rising, switching protocols numerous times got it down again and again. The latest unique protocol he did get his psa down to .007 which within his parameters and history of PCa is unheard of. (Gleason 9 patient, too)

His story is going to be posted at www.yananow.org (soon) will post link when it is up and running. I am going to try the same protocol even with much higher psa level and see if it atleast drops my psa significantly and there are 4 others or so also trying this out right now. We will see how this pans out.

Just a note Allen, You stated Zytiga and Xgeva as new hormonal therapies and I believe you meant Zytiga and Xtandi. Xgeva is not a hormonal therapy but rather a skeletal event inhibitor.

Also in the very near future we will be adding another new hormonal therapy drug in TAK-700 (Orteronel) that could be a potential step up in performance and replacement for bicalutamide.

Tony

UPDATE on my hubby's application for the clinical study of GTx-758. Dr. Flaig just called and said that Marshall's blood work showed a "low threshold" with regard to blood clotting so he is not being accepted in this study. The depression in our house right now is heavy.

Dr. Flaig says he now wants to put Marshall on Zytiga & Prednisone, but he feels there are issues with Medicare paying for it -- so we will see what the next few days bring.

I will now try to find some threads concerning Zytiga.....

Marilyn

Allen,

Thank you so much for the info. I will definitely read all of these links and talk to Marshall, as well as the doctors. Sometimes a setback can really get into your brain and for a bit of time you feel helpless and hopeless. Then I get on this site and read all these stories and the perspective changes dramatically.

THANK YOU!
Marilyn