Casodex/Bicalutamide or MDV3100/Enzal... - Advanced Prostate...

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Casodex/Bicalutamide or MDV3100/Enzalutamide can lead to promotion rather than suppression of Prostate Cancer Metastasis

Mascouche profile image
40 Replies

Just came across this study that seems like quite an important finding for those of us who might be taking or have taken Casodex/Bicalutamide or enzalutamide. The study is here: ncbi.nlm.nih.gov/pmc/articl... and it explains that those two drugs can reduce the size of the primary tumor and can decrease PSA levels while on the other hand they increased metastasis in some patients!

Since a tumor to the prostate is unlikely to kills us by itself and neither does PSA, and because metastasis can hurt and kill you eventually, I figured that this article from November 2020 is good knowledge to have.

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Mascouche profile image
Mascouche
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LearnAll profile image
LearnAll

This chinese study is alarmist ...it says "In Some Patients" Means it does not happen in most patients.The cheapest and quickest way to check bone mets is to do Total ALP (or even better.. Bone Specific Alk Phos) along with PSA. By checking both PSA and Bone ALP, you can't miss if mets are growing.

Bone ALP starts rising EVEN BEFORE bone mets show up on conventional imaging scans.

maley2711 profile image
maley2711 in reply to LearnAll

re ALP and PCa,

" A total of 63 studies from 54 articles with 16,135 patients were included in this meta-analysis. The pooled results indicated that high baseline ALP was associated with obviously poor OS (HR=1.74, 95% CI: 1.47–2.06) and PFS (HR=1.60, 95% CI: 1.13–2.26) in patients with PCa. The pooled HR for bone-specific ALP and OS was 1.76 (95% CI: 1.45–2.15). However, no association between ALP and CSS (HR=1.002, 95% CI: 0.998–1.005) was found for PCa. The results of subgroup analyses were all in accordance with the main findings. Sensitivity analysis suggested that no single study could affect the stability of the results.

ncbi.nlm.nih.gov/pmc/articl...

2018 meta-analysis. While there is an association between ALP and PFS and OS, note that there is no association between ALP and PCa for CSS. This study does mention any conclusion re high ALP and proven metastases, though there may be that association. Perhaps someone has a link for some conclusion on that issue?

dhccpa profile image
dhccpa in reply to LearnAll

Not familiar with ALP. Is it a blood test? Perhaps it's being run and I have no idea of its purpose. Thanks!

LearnAll profile image
LearnAll in reply to dhccpa

BALP or Bone Alkaline phosphatase is an enzyme released in quantity according to how much your bones are being repaired. Indirect measure of how much bone is damaged.If it is in normal range then, your mets have healed and cancer cells in bones are not growing.

dhccpa profile image
dhccpa in reply to LearnAll

I believe ALP is being measured on my frequent blood tests. Same thing as BALP? I'll check into that. MO has never mentioned but what else is new?

Tall_Allen profile image
Tall_Allen

It's not important at all. It's just a lab study from 2013.

Clinical studies (in humans, not mice) have proven that enzalutamide reduces progression and increases survival in metastatic men.

Mascouche profile image
Mascouche in reply to Tall_Allen

I accidentally put the old link from 2013. Here is the article with the correction from Nov 13 2020: pubmed.ncbi.nlm.nih.gov/331... and there is also this link ncbi.nlm.nih.gov/pmc/articl... which also says Nov 13 2020 at the top.

Tall_Allen profile image
Tall_Allen in reply to Mascouche

It was just a correction to the 2013 article, not a new 2020 article. The correction was this: "For Fig. 5E, in the last row stained for PSA, one of the images in the MDV group was mistakenly inserted as the ASC group with a vertical translation during article preparation. The correct images from the MDV group and ASC group are presented in the corrected figure. We sincerely apologize for the error, and we assure that the correction of the images will not alter the original results or conclusions."

jbc.org/content/295/46/1579...

It's still a useless lab study that patients should ignore.

LearnAll profile image
LearnAll

Also, what enzalutamide does....can also be done by Bicalutamide....with less side effects. After all, Both Bicalutamide and Enzalutamide are Anti Androgen meds.

Roscoaus2000 profile image
Roscoaus2000 in reply to LearnAll

Like every comment, every person is different. Bialutamide very successfully lowered my psa from 9000 to <.01 in 4 months . It resolved all cancer in tissues and reduced the size of my hundreds of skeletal Mets. After 12 months psa increased to 2 and I changed to Enzalutamide. My night sweats vanished and my energy levels soared. Unfortunately after 4 months the drug passed the blood brain barrier and I had a minor seizure. I then changed to Aberiterone for the last 32 months and my psa is still only .03. However, energy levels have dropped. Three different side effects! I would add that I have 3 monthly Zoladex and Xgeva injections. I also take daily supplements, Curcumin, bilberry, calcium and vit. D. At 80, I am happy to say I am 4 1/2 years from medical intervention and 15 years since I refused a biopsy at psa 7.

maley2711 profile image
maley2711 in reply to Roscoaus2000

At what point were you diagnosed......when you were already symptomatic? Did you ever have primary treatment of prostate.? Have you ha any 2nd thoughts about ignoring your high PSA at age 65?

Roscoaus2000 profile image
Roscoaus2000 in reply to maley2711

Well I went 10 years with no symptoms. Life was good. Body was good. Sex life was good. At 75 I started to have rheumatic pains in my back, which I suspected was age related. At 76 I found I could control condition with diet. At 76 1/2 the pain became intermittent. Good days and bad days. A CT scan confirmed metastatic prostate cancer. I had a 6 month period when I was weak and lost bladder control after treatment started. Since then life has been good. However, the ADT has taken away my manhood. This is ok since at the time my wife’s diabetes caused loss of sexual interest as well. We have a good relationship and will celebrate 60 years in May.So no, when I compare myself with other 65yo who have gone the standard surgical treatment, chemo and side effects I consider myself very lucky.

j-o-h-n profile image
j-o-h-n in reply to Roscoaus2000

"We have a good relationship and will celebrate 60 years in May"

Remember you can always shake hands...... but wash them first (20 seconds while singing happy birthday)...

Good Luck, Good Health and Good Humor.

j-o-h-n Saturday 01/09/2021 1:30 PM EST

monte1111 profile image
monte1111 in reply to j-o-h-n

"You'll pardon me if I don't shake your hand." Mr. Robinson - The Graduate.

j-o-h-n profile image
j-o-h-n in reply to monte1111

Hey Hey........

Good Luck, Good Health and Good Humor.

j-o-h-n Saturday 01/09/2021 3:58PM EST

monte1111 profile image
monte1111 in reply to j-o-h-n

You aren't one of those agitators, are you?

j-o-h-n profile image
j-o-h-n in reply to monte1111

You mean a white bald headed Nazi supremist with tattoos all over his body no front teeth and owns a pickup truck a fully load AK47 and has 4 pit bulls and can scale buildings..... Nope.... never heard of em......

BTW Mr. RobinGson, you're trying to seduce me.....

Good Luck, Good Health and Good Humor.

j-o-h-n Saturday 01/09/2021 4:34PM EST

GeorgeGlass profile image
GeorgeGlass in reply to j-o-h-n

What about the white anarchist with bombs, eggs, lasers, water bottles and guns shooting innocent people or black dread locked Marxists with gold teeth looting, burning down buildings, hitting old ladies over the head with bats, shooting police and children quietly walking down the streets out sitting on a car? That type of agitator? Many have not heard of them either.

maley2711 profile image
maley2711 in reply to Roscoaus2000

when you refused biopsy at age 65, was your decision based on any scientific evidence? or just that your philosophy was...I feel fine, no symptoms, why risk side effects from any treatment, I'll take my chances?

Roscoaus2000 profile image
Roscoaus2000 in reply to maley2711

My main motivator was fear of infection. At that time the media was full of superbugs and that the antibiotics were no longer working. The examples in media were of a person being infected during a prostate biopsy and dying from superbug infection. On top of that there was much controversy about psa testing. The chief of AMA said publicly that he would never have a psa test. I asked my MD if there was anything else I could do. He said “watchful waiting”. We did that, taking regular psa tests. He never warned me that the progressive rise, 7,12,15,27 was dangerous. When we moved house and went to another doctor, I read his report that said I had refused any treatment. I thought I was only exploring alternatives. At that point I said, well I am doing well, let’s wait until I get some symptoms.I wouldn’t recommend this action to anyone now, but here I am. Alive and well.

maley2711 profile image
maley2711 in reply to Roscoaus2000

Your 1st Doc watched as your PSA continued to rise to levels that could only be explained by cancer or severe infection....and he never alerted you that this was likely significant cancer? and that same Doc charted that you refused treatment, when he never advised that you have biopsy as PSA rose over 10?? If that is true, clear-cut case of malpractice!! I have PSA of approx 7 at age 72, tried but failed(pain!) to have a biopsy done 6 weeks ago....MRI shows very concerning lesion. I KNOW that my Doc is most concerned about rising PSA.....mine has been mostly the same for past 2 years.....and in 7 years has risen from 4.1 to 7.....some part of that explained by very enlarged prostate.....at least double the volume for an average man at my age.

thank goodness these non-interventional drugs have worked for you so far...for so many, they don't. I assume you never did have surgery or radiation, as cancer had escaped prostate?

Roscoaus2000 profile image
Roscoaus2000 in reply to maley2711

You are correct. I don’t think he did well. However, after comparing myself with others who have gone the conventional route I feel blessed. No ,I have never had any surgery nor Chemo. I went straight to what is officially termed Palliative care. Being told that by my Oncologist was a big shock as I had visions of a poor feeble old person being spoon fed. I now understand it is a standard description. Yesterday I played golf with my 55 yo som and my 25 yo grandson. Next week I hope my 8 yo great grandson will play.

maley2711 profile image
maley2711 in reply to Roscoaus2000

I want to be clear in my undrstanding...initially, at PSA 7 , your Doc advised biopsy, but you refused....then, as your PSA progressed, you had consultations with your Doc, but he did not repeat his advice to have a biopsy?? Refusing biopsy is essentially refusing treatment, so if that is actually what transpired, then your Doc's "refused treatments" would probably be defensible. If he never agin advised biopsy, then IMHO he was negligent at the least!! There is a good chance that a biopsy could have led to a successful treatment.....meaning you could have escaped the ADT and its side effects, ..though you don't mention the extreme life threatening SEs so many men suffer with ADT. Yes, be thankful that your reached 80...you rolled the dice and mostly won.....wonderful you can still enjoy a good walk with son and grandsons!!! Best Luck for another 10 years!!

Roscoaus2000 profile image
Roscoaus2000 in reply to maley2711

I didn’t realise I was refusing a biopsy, I thought I was exploring alternatives, which I thought he was agreeing to. He suggested the watchful waiting. Subsequent consultations seemed to me to be just routine recording of rising psa. Shortly after we moved and with me worrying about my wife’s health I ignored my own as I had no symptoms. It was not until my 75 birthday driving medical with a new doctor that I became aware of previous doctors comments. My psa then was 1350 and my md certainly urged me to have further specialist tests. It was at that point I chose to decline. It was another 18 months until my symptoms became really troublesome that I sought advice. The chemical castration and ADT have certainly worked well. Overall I have only had about 6 months of pain etc. On balance I think I have come out ahead of average. Only one of my 5 paternal males and 3 females and none of my maternal male and 4 female ancestors have lived as long and healthy lives as I have enjoyed.

maley2711 profile image
maley2711 in reply to Roscoaus2000

Yes, thank goodness for your good luck..I'm sure statistics would confirm your luck!!! I'm still shocked that your 1st Doc did not repeatedly advise a biopsy!! I guess that is another strategy..refuse biopsy and ask for bone scan instead!! Or, nowadays, other scans, are even more accurate for seeing metastases.

Roscoaus2000 profile image
Roscoaus2000 in reply to maley2711

I knew so little about prostate cancer in 2005. The advice on the net was much less then. Also much controversy over psa. I know much more now! I think with so much more drug sponsored advice now I doubt I would have taken my course. However, given my positive experience I am not sure I haven’t, luckily, taken the best road. Incidentally, here in Australia, I doubt you could refuse anything other than the standard treatment, unless you were independently wealthy. Our medical system is wonderful for anyone on the aged pension who owns their own home. Our Safety net ensures that you do not need to spend more than $700 a year on medical expenses if you are not in a Private health fund.

maley2711 profile image
maley2711 in reply to Roscoaus2000

Nice to converse with an Aussie....some good movies from your place!! BTW, I don't understand " I doubt you could refuse anything other than the standard treatment, unless you were independently wealthy." Does this mean "I doubt you could afford anything other than standard treatment, unless you were wealthy"

Yes, the internet is such a wealth of info....if you can sort out the good from the bad. I imagine we patients can be pains in asses for the Docs now!! Thankfully, I have a Doc who, out of the blue, stated that I should consider him as my consultant!! He had become aware that I did much outside reading!! Still, when there is a fork in the road, I usually decide on following his advice...sometimes with reservations. With his medical organization, he is not overly incentivized to advise something that would

pad his organization's bank account . In fact, the opposite may be true? I would be interested in comparing the Aussie and American medical systems....is there as much controversy there as there is here re changing the system?

Roscoaus2000 profile image
Roscoaus2000 in reply to maley2711

We have a Medicare system which prescribes the fee for service. Tax payers pay 1% extra to cover the cost. We also have a private health care service that you can subscribe to about $4000 pa.Medicare system is free. Hospitals are wards. There are fewer doctors and specialists in Medicare so for some procedures there is a waiting list. However, for Cancer there is great service. I don’t have private care and it costs me nothing except standard fee. Max $700 per year for prescriptions and medical fees. No one is ever bankrupted for cancer treatment. If you are a privately funded pensioner it could be much more expensive.

maley2711 profile image
maley2711 in reply to Roscoaus2000

what sort of tax pays for that system? a dedicated tax...or from general revenues?

dhccpa profile image
dhccpa in reply to Roscoaus2000

What is the purpose of the bilberry?

Roscoaus2000 profile image
Roscoaus2000 in reply to dhccpa

Bilberry is a good blood vessel support, mainly recommended for eye health.

GeorgeGlass profile image
GeorgeGlass in reply to Roscoaus2000

were you taking ADT with the casodex?

what do you mean when you say: "3 monthly Zoladex and Xgeva" - is that one zoladex and two xgeva?

were you more susceptible/vulnerable to a seizure on the xtandi? isnt the side effect amount for seizures only in about 1% of men on xtandi?

Roscoaus2000 profile image
Roscoaus2000 in reply to GeorgeGlass

For 4 years I have been taking 3 monthly injections of Zoladex. I took Casodex daily until it stopped working. Then I changed to daily Xtandi until I had a seizure. Since then I have taken Zytiga with Prednisolone daily.For 18 months I had Xgeva injection monthly. Since then I have had it 3 monthly.

The vitamins I mentioned I have taken daily for years.

I may have misunderstood the term but I understood that the Zoladex (Casodex-Xtandi- Zytiga, Prednisolone) combination was called ADT.

Mascouche profile image
Mascouche

This article from 2016 goes along the same lines too. pubmed.ncbi.nlm.nih.gov/270... says:

"Early studies suggested that prostate cancer (PCa) stem/progenitor (S/P) cells might play key roles to promote the tumor initiation and metastasis. Yet their linkage to the failure of androgen deprivation therapy (ADT), however, remains unclear. Here we demonstrated that the ADT with anti-androgens Casodex (also known as Bicalutamide) and Enzalutamide (also known as MDV3100), but not the newly identified AR degradation enhancer, ASC-J9(®), increased PCa S/P population, which might then lead to enhance the PCa cell invasion. Targeting AR with ASC-J9(®), and not targeting androgens with Casodex or Enzalutamide, led to suppress PCa S/P cell invasion. Mechanism dissection revealed ASC-J9(®) could suppress S/P cell invasion via altering the EZH2/STAT3 and/or AKT/EZH2/STAT3 signals. Together, these results suggest that targeting PCa S/P cells with ASC-J9(®) or inhibitors to interrupt the EZH2/STAT3 and/or Akt/EZH2/STAT3 signals may become a new therapy to overcome the unwanted side effects of Casodex or Enzalutamide to further suppress the PCa metastasis."

Has anyone tried ASC-J9 ? Is it safer than Casodex? I know that Casodex is considered safe by most but since (amongst other things) I have suffered of breathing issues, cognitive issues and a severe loss of weight (15lbs in just over one month) so it is not safe for me. So I am also looking for something else. From what I am reading, it is unlikely to be Enzalutamide if that can causes a spread of metastasis despite a lowering of the PSA. But maybe ASC-J9 ?

Tall_Allen profile image
Tall_Allen in reply to Mascouche

It's still just a lab study.

ASC-J9 is not a direct anti-androgen like enzalutamide, or even a weak anti-androgen like Casodex. It is a chemical based on curcumin that may have some useful properties acting on the androgen receptor, although it hasn't been tested clinically. It is purely investigational, and is not available to patients.

In the US, there is a lab at the University of Rochester that has been working on it for years, but they have never started a clinical trial. If you are interested, you can ask them why.

If you are interested in an alternative ADT medicine, you can try transdermal estrogen. Several men on this forum use it, and it has a long history of being a clinically effective treatment for prostate cancer.

Mascouche profile image
Mascouche in reply to Tall_Allen

Thanks for the info Tall_Allen. I've recently heard about testosterone injections (either by itself or in rotation with Lupron) and also of estrogen patches. I assume transdermal estrogen is the same thing as the estrogen patches? I also stumbled unto an article about Aromatase Inhibitors a little earlier. Seems like that too might be a possible avenue for me to explore further. Have you ever heard of Aromatase Inhibitors and if you did, do you have an opinion on them?

Tall_Allen profile image
Tall_Allen in reply to Mascouche

Aromatase inhibitors is the opposite of transdermal estrogen, and is a very bad idea. BAT may work in some cases; but it often makes it worse - it should only be done in a clinical trial.

Mascouche profile image
Mascouche in reply to Tall_Allen

Thanks

j-o-h-n profile image
j-o-h-n

"promotion rather than suppression"

Holy chit, fxxked again....

Good Luck, Good Health and Good Humor.

j-o-h-n Saturday 01/09/2021 11:52 PM EST

4Rosebud profile image
4Rosebud

thanks, i've heard the same thing...what are you doing and whats your situation.

I have used cazadex for 2 months but didn't help and 1 firmagon injection when my psa was 199 brought it down and now almost

2 1/2 years of lupron..and zytiga, but my tendency is to do everything I can to use alternatives, as long as possible.

I'm using misletoe injections (approved in UK) should be here but big pharma...you know... and cbds, vitamin c infusions, ozone theraphy, diet, exercise, certain supplements and have had great luck controlling it. my psa was 2 and 3 xing every month now its been 2 years and still low 20's.

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