A study of patient's choice of ADT: b... - Advanced Prostate...

Advanced Prostate Cancer

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A study of patient's choice of ADT: bicalutamide, a gonadotrophin-releasing hormone analogue or orchidectomy

George71
George71

As the title conveys, All three are a different form of ADT... merely because a person has circulating testosterone in their blood when taking bicalutamide doesn't mean bicalutamide is not a form of ADT or that they are able to use the testosterone even though they have it.

My understanding is -- the way it was explained to me:

bicalutamide blocks you from being able to use testosterone. When a patient is being switched back and forth from lets say 6 months of lupron to 6 months of bicalutamide --there is no off period of ADT -- they are still on ADT either way -- just a different form of ADT.. (a different way of denying your body testosterone) Lupron stops you from being able to make testosterone -- whereas bicalutamide doesn't stop you from making testosterone but -- blocks the cells from being able to use it ... in effect resulting in the same thing ( ADT)

--- lupron -- no ability to make testosterone -- therefore no testosterone to use. ----bicalutamide blocks ability to use testosterone. even though you can still make testosterone and have testosterone circulating in the blood..

Testosterone circulating in the blood while on bicalutamide means virtually nothing --- you might as well not have it -- you cant use it.

bi-polar treatment can be done on lupron but not on bicalutamide. While on bicalutamide you can inject all the testosterone you want -- but the body is blocked from using it --

pubmed.ncbi.nlm.nih.gov/162...

161 Replies
oldestnewest

Hi George71,

Prepare for the incoming posts about ADT use.......from all the online experts interested in these treatments. I’m particularly interested in this subject since the ADT biz is probably the most

promising source of potential long term advances in the treatment of PCa. However, because of the big money involved with these drug developments, guys need to be

very careful choosing their MOs because many will be influenced by representatives from Big Pharma and the restrictions placed upon their choices by the business administrations at the organizations where those MOs are employed. Read, read, read.......

Jeff

Have NO BIG PHARMA influencing me since the get go because I went with castration. 95% of my own body producing "T" ability GONE and NO DRUG INDUCED SIDE EFFECTS able to occur. Get my "T" from a non-DNA compliant injected method. Any other Gleason 10 Unique Eunuchs' out there??? Following injection I have 1,600+ ng/dL as per testing and life isn't too bad.

I’m a bit confused. Why would you have an operation to prevent producing T then take a injected form of T?

And who makes the injected method? Not big pharma ?

At time of diagnosis by urologist's biopsy I chose NOT to have ADT so Orchiectomy was it. At initial meeting with treating doctor HE said he would begin TRT after treatment, I said OK. Method was left up to me and decided on injection.

Ok that makes sense now! So you have finished all treatment? Is your prostate still intact! How’s your psa ?

My 2015 Cryo was initially to be 1 treatment of entire prostate but due to procedure change it needed 2 treatments and then the immuno. Prostate still remained and minor recurrence in 2018 required more cryo. PSA continues to fluctuate.

gregg57
gregg57 in reply to Stevecavill

BIG PHARMA bad.

George,

Bicalutamide blocks testosterone from acting on Androgen Receptor WITHIN the prostate gland. The testosterone is available for all other purposes...that's why people who are on Bicalutamide have high energy, less fatigue, almost no hot flashes and some sexual life. Because their blood has plenty of Testosterone circulating without stimulating Androgen Receptor .

Lupron deprives the entire human body of testosterone causing side effects everywhere in the body.

Please do not stop Lupron as bicalutamide monotherapy is suitable only for a very small fraction of people with PCa.

George71
George71 in reply to LearnAll

LearnAll,

thanks, I see the distinction you are making..

" testosterone is available for all other purposes"

It would seem (and i am not saying I have had an in depth talk with any authority on this either but) -- bicalutamide would have to be magic to only go and occupy A/R only on prostate cells. It occupies A/R anywhere it finds them.

But --- be that as it may -- at any rate

When switching from lupron treatment to bicalutamide treatment you are still on ADT.

And at least as far as the prostate cells and PCa is concerned it is doing the same thing just differently.

So it isn't an OFF period from ADT as far as the PCa cells are concerned -- and bicalutamide leads toward the same mutating end.

As for side effects -- I've read that they are less with bicalutamide because the amount taken is not able to occupy every A/R receptor in the body - even at doses of150 -- which is the highest prescribed dosage. And it is simply not as effective. It is more likely to cause man boobs because the blood has all this testosterone floating around it can't use and thinks it is making too much and off set with raisng estrogen levels.

As I said above all this is just my conception -- It may in fact be all wrong -- that is the reason for the post -- to hear from those how may point us to the study or article that can answer these thoughts.

George71
George71 in reply to George71

On bicalutamide your testosterone levels go up because the body is being starved of testosterone and so it keeps making more T.... T it is unable to be used because it is being blocked by the bicalutamide. therefore more blood testosterone floating around with very few places it can find to go to .. If your testosterone was being used normally in all other cells you T levels would be back around 300 / 400 or so -- but it doubles..

Bethpage
Bethpage in reply to George71

Except that my husband has been on bicalutamide since Feb. 2019 and has had a lower testosterone reading every 3 months. PSA before last was 45. Two weeks ago was 17. He is on bicalutamide 50 mg only, his choice because of cognitive impairment.

George71
George71 in reply to Bethpage

thanks Bethpage,

bicalutamide is not thought to lower testosterone production ... maybe it is something else your husband is taking that is doing it.

Bethpage
Bethpage in reply to George71

Would have to be tamoxifen (no) or bendustamine rituximab (don't think so as it's chemo) - or older age (most likely?). He's taking nothing else.

ragnar2020
ragnar2020 in reply to George71

Hi George71,

What I hope to see in this string of posts is a detailed explanation of how ADT drugs have been used for PCa care by various guys and their experiences with those ADT drugs and their related SEs. Much has already been written about this. These sort of personal experiences are always helpful for alot of guys reading this forum.

Also, it will be interesting to see some feedback from guys who have decided to forego the use of the ADT drugs produced by Big Pharma and use dermal estrogen (tE2) patches or gel or both to drive down their testosterone. Several guys on this forum are using tE2 for their ADT. But since the use of tE2 is not endorsed by MOs who follow the NCCN SOC guidelines for ADT drugs, the use of tE2 is occurring in the UK, Canada, Aust, and the EU, but it is no longer available in the US. The SEs of tE2 are supposedly less than with SOC ADT drugs, but that'll be something I hope will be elaborated upon here.

Off we go.......

Jeff

George71
George71 in reply to ragnar2020

I completely agree with all you said --- they have been doing this for 60 years with little to show ,,, ADT has its place but it isn't the be all that ends all ...ADT while on another treatment -- like radiation to kill PCa cells visible in bone / lymph nodes etc but not as a meaningful therapy -- it seems like it just masks the problem or is palliative but when the CRPC comes it all catches up. ... Even if CRPC there is still a lot of hope for those guys -- if they can find a doctor who will keep on helping them fight -- Thank God for doctors like these that will keep fighting for all of us ..

One of the most inspiring comments in Dr. Kwon's video is "don't stop fighting" --- to that I say .. we aren't -- don't you !!! Don't quit on us.

Stevecavill
Stevecavill in reply to George71

It hasn’t had “little to show” at all. What do you think has driven up the survival rate massively?

RSH1
RSH1 in reply to George71

I took bicalutamide for a month. I did ADT (estrogen based) for 5 months. I did SPT for 12 months and counting.

My libido on ADT was zero.

My libido on bicalutamide was almost zero but seemed like there was something.

My libido on T is great. For the first month or so it was about where it was when I was in my 20s. After that it tailed off and I'm maybe good for once or twice a week. (my endogenous T shut off?)

Muscle gain: ADT huge muscle loss

Muscle gain: bicalutamide. I did this after the 5 month ADT so muscle was about as low as it was going to go. I didn't notice much muscle growth on bicalutamide.

Muscle gain: SPT. Wow! In a week I put on 5 lbs of lean mass. Tapered off but in one year it was just under 25 lbs lean mass and over a percent of fat loss (my bodyfat is quite low so one percent is pretty significant).

It's possible that I wasn't on bicalutamide long enough to see muscle gain or libido effects.

George71
George71 in reply to RSH1

You won't get much muscle gain if any on bicalutamide -- it is blocking A/R on cells from getting it anywhere it finds them -- in the brain and certainly in the muscles and you have hundreds of lbs. of muscles all needing T ... the walnut P gland only takes up a little bit of our T..

RSH1
RSH1 in reply to George71

Precisely what I think. But because I only did bic for a month, I didn't want to conclusively say that I would have less muscle loss than on ADT.

MateoBeach
MateoBeach in reply to RSH1

Just to mention I am joining the Supra Phys-TRT this week. Currently off all ADT as PSA is currently low and stable following PLN RT with 6 mo estradiol ADT. But have the full spectrum of hypogonagal symptoms. Including very low muscularity despite active workouts and 12% body fat due to keto diet and intermittent fasting regimen.

Not sure what is best regimen for TRT for HSPC, high or Very high and whether to cycle occasionally as all the BAT data is for CRPC. What is best for preventing emergence of castrate resistance (as per Bob Leibowitz theory)?

George71
George71 in reply to MateoBeach

MateoBeach,

In my opinion you should do continuous Super Testosterone ... low testosterone results in PCa cells mutating into testosterone independent cells --- normal testosterone slows that process some what ... super high testosterone causes death in PCa cells with double strand breaks of their DNA ... does not harm healthy cells. super t apparently clogs up the cells making them unable to complete the cellular process of expelling the t in order to start another splitting (doubling) cycle..

MateoBeach
MateoBeach in reply to George71

Thank you George. Yes I am planning on supraT. But also wonder if eventually a sub population of PC cells will become adapted to even that. Thus question if occasional breaks to very low /castrate T could be beneficial to clearing the decks. Sort of like BAT but much slower at longer intervals. (Several months?) I cannot find much data about this in hormone sensitive disease. Perhaps just following PSA response as the indicator may be the best we can do.

MateoBeach
MateoBeach in reply to George71

Also planning on tamoxifen instead of an AI per T_A’s advice and data. But wonder how high estradiol might go and if any concern there besides gynecomastia prevention?

RSH1
RSH1 in reply to MateoBeach

I agree with George71. SPT is needed. Just high-normal T wouldn't be good.

One thing to add though: monitoring PSA is critical. You might see a PSA flare for the first month. After that it should die down. And PSA is not prostate-specific. So you might have a low level produced by other cells. Maybe 0.01-0.03. And PSA is not cancer progression. It's a good insight to cancer growth.

But if there are, say, a million cancer cells, and they produce 1 unit of PSA when T is low, when T goes high the same million cells will be stimulated to produce, say, 2 units of PSA.

Sounds like you're doing a similar plan as I have done. I did 5 months of estrogen ADT, 1 month of bicalutamide/dutasteride, and 12 months and counting of SPT.

I have a blog with my current plan. Important to use an AI, maybe keep DHT in check, same with prolactin. Possibly increase progesterone for a few months and then let go to normal levels.

1,2,3,10,11 are components of my hormonal plan: prostatecancer.health.blog/...

MateoBeach
MateoBeach in reply to RSH1

Thanks. I will check that all out. Gets complicated when considering adding the AI (vs tamoxifen) and other components.

I noted in the LNCaP tumor study in athymic mice that finasteride blockade reversed the benefit of the high T! Very surprising. Apparently DHT is required.

George71
George71 in reply to MateoBeach

see RSH1 explaination to me on another post below:

Arimidex gave me bad ankle swelling. So did anastrazole. So I use letrozole. No bloating. (I went each AI and then going off, then on, then off to verify that it did appear to be the AI that was causing the bloating).

I used Tam for a few weeks. When my SOC oncologist found out she begged me to stop because she feared cardiac issues for me.

Letrozole 1.25-2.5 mg/wk has worked for my moobs. I no longer have to use my wife's sports bras!

George71

George71 in reply to RSH1

3 hours ago

Did you have mild boobs and Letrozole 1.25-2.5 mg/wk cleared them up? or no boobs and it keeps you from getting them?

RSH1

RSH1 in reply to George71

1 hour ago

I had moobs that were big enough that I had to use my wife's sports bras. I can't be 100% certain that letrozole cleared them up. I changed from estrogen to bic to t. They were definitely growing during the estrogen and didn't seem to get any smaller on my month of bicalutamide. When I started T I started the AI. They went away.

George71

George71

2 minutes ago

Thanks, good news ! I will ask to switch to Letrozole 1.25-2.5 mg/wk on next appt.

MateoBeach
MateoBeach in reply to George71

Yes I did read that. Good info. If I go with an AI I will request letrozole. Also like the once weekly dosing at 2.5 mg.

George71
George71 in reply to MateoBeach

That is interesting --I'm currently taking Avodart / every other day

MateoBeach
MateoBeach in reply to George71

This study was referenced in one of the Leibowitz publications and videos on SPTRT, so I went looking for it .

(Full text pdf also available) ncbi.nlm.nih.gov/pmc/articl...

"Removal of TP or implantation of finasteride, a 5 alpha-reductase inhibitor, in nude mice bearing TP implants resulted in the regrowth of LNCaP 104-R2 tumors." . .

"Although androgen ablation has been the standard treatment for metastatic prostate cancer for > 50 years, our study shows that androgen supplementation therapy may be beneficial for treatment of certain types of human prostate cancer and that the use of 5 alpha-reductase inhibitors, such as finasteride or anti-androgens, in the general treatment of metastatic prostate cancer may require careful assessment."

George71
George71 in reply to MateoBeach

Am I reading that wrong --" the removal of the implantation of finasteride resulted in the regrowth of LNCaP 104-R2 tumors. "

That sounds like finasteride, a 5 alpha-reductase inhibitor was suppressing growth ...?? Also I think Dr. Leibowitz leaves you on Avodart when he starts superphyl testosterone.. I have had 2 phone conferences with them. Dr. Esg.

RSH1
RSH1 in reply to George71

Please let me know what he says. I thought we should block DHT when on SPT. If I'm wrong and we should let DHT fly that's great (two more meds I don't have to take). DHT targets would be nice. I think 5-10% of T is converted to DHT. I have a T avg of 2500. So that would be DHT of 125-250. That's assuming the T->DHT conversion isn't a declining exponential.

George71
George71 in reply to George71

Also my son (40 years old) uses a sports Dr. for his testosterone --( he takes it for general good health no cancer) -- his Dr. told him there was no evidence to support testosterone causing prostate cancer but he had concluded from his research that DHT may in fact be the culprit -- caused by rising estrogen in men. He believes that to off set this our body converts the low testosterone to DHT a much more high octane fuel if you will. I have experienced a PSA drop of about 25% while on Avodart (on and off over the last 2 years) that is the only thing I have taken other than natural vitamins supplements no (rarely ever) eggs etc

RSH1
RSH1 in reply to George71

I'm going on vacation today so this article will provide a little light reading :)

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

George71
George71 in reply to RSH1

Thats outdated Oct 2019 -- LOL --- have fun on vac.

who do they think they are -- doctors ??? LOL

Payel Chatterjee,1 Michael T. Schweizer,2,3 Jared M. Lucas,1 Ilsa Coleman,1 Michael D. Nyquist,1 Sander B. Frank,1 Robin Tharakan,1 Elahe Mostaghel,2,3 Jun Luo,4 Colin C. Pritchard,5 Hung-Ming Lam,6 Eva Corey,6 Emmanuel S. Antonarakis,7 Samuel R. Denmeade,7 and Peter S. Nelson corresponding author1

MateoBeach
MateoBeach in reply to George71

This says to me that the observed effect of high T to cause destruction of the tumors on the mice - causing them to involute, necrose and fibrose - was reversed by finasteride implants allowing the tumors to regrow. This implies that the benefits of high testosterone on these PC tumor were nullified if/when the conversion to DHT was blocked by the 5-a-reductase inhibitor.

So for LNCaP cell tumor exografts the benefit of supra-T levels requires the conversion of some of it to DHT. Yes it is very interesting and strikes a note of caution regarding including finasteride or dutasteride in a supraphysiologic T strategy for PC. It will be interesting to here the response of Bob Leibowitz on this.

Of mice and men, therein is the rub: How applicable is this result?

George71
George71 in reply to MateoBeach

help me with this --- "Removal of TP or implantation of finasteride, a 5 alpha-reductase inhibitor, in nude mice bearing TP implants -- resulted in the REGROWTH of LNCaP 104-R2 TUMORS." . .

Doesn't that say -- if you REMOVE either the TP or REMOVE the implanted 5 alpha-reductase inhibitor, (Finasteride) from the rats bearing the TP the TUMOR REGROWS .... in the alternative --- If you insert finasteride in the rat with TP the tumor will shrink or go away...

Therefore finasteride inhibits cancer growth by blocking some of the DHT.

Isn't that right -- or am I missing something? Help me.

George71
George71 in reply to George71

If you remove the finasteride from the rats and the cancer REGROWS then the finasteride is blocking the cancer from growing ---yes ? -- no?

George71
George71 in reply to George71

I think what it says is they implanted TP and a finasteride, pellet a 5 alpha-reductase INHIBITOR in mice that had PCa tumors -- when EITHER the TP or the 5 alpha-reductase INHIBITOR (finasteride) were REMOVED from the mice the TUMOR REGREW .

MateoBeach
MateoBeach in reply to George71

No. In a full-text subheading: Androgen-Dependent Remission of LNCaP 104-R2 Tumors and Its Reversal by Removal of the TP (Testosterone propionate Pellet) or Implantation of Finasteride." Adding Finasteride implant had the same effect as removing the testosterone pellet., allowing the tumors to regrow.

I know, it is surprising for me too. Suggests that it requires the presence of DHT in order for the tumor destroying effects of Supra-T to work. I recognize this is not consistent with Dr. Bob L's program. Perhaps his results could be even better without the 5aRIs. Or perhaps this animal model is working differently than human PC.

George71
George71 in reply to MateoBeach

Thanks. I will try and research further -- I consulted with them twice -- and when I talk again I will ask them where they stand on this. I may know something in a week or so -- i will email for an answer ... Dr. Eshg. said I could call him in a couple of months and talk again -- I will message you or post it if I get an answer --- remind me to follow up if you don't hear something in a week or so.

George71
George71 in reply to George71

full-text subheading: Androgen-Dependent Remission of LNCaP 104-R2 Tumors and Its Reversal by Removal of the TP (Testosterone propionate Pellet) or Implantation of Finasteride."

I can see how you can interpret it both ways ... It still seems to say to me --

REMISSION of tumors is REVERSED by REMOVAL of the testosterone OR finasteride pellet ..

When they (testosterone and finasteride) were in the mice the tumor was in remission. If either/or -- was REMOVED the tumor REGREW...

noahware
noahware in reply to LearnAll

I think that is mostly right, but I don't think the blocking is limited ONLY to prostate and PC cells. I think those tissues are just where AR is most highly expressed.

One article notes "The Androgen Receptor (AR) is a nuclear receptor (NR) which responds to the hormones testosterone (T), and dihydrotestosterone (DHT), by modulating gene expression in a variety of cells including prostate and muscle tissue. "

So while on bicalutamide I think my T is available for some uses but not all, and might I expect a potential loss of muscle mass even with high serum T levels? Not sure. (But not so far for me, that I can tell.)

It seems to me if the mechanism of action was that precisely limited, to prostate cells only, the med would be called a "SARM" (selective androgen receptor modulator) and be analogous to a "SERM" (selective estrogen receptor modulator) that block estrogen only in certain cells but not in others. (Like the tamoxifen I take to prevent my high level of E2 from promoting more growth of breast tissue.)

Each estrogen receptor has a slightly different structure, depending on the kind of cell it is in. So breast cell estrogen receptors are different from bone cell estrogen receptors. But what about AR structures? I don't know if the same phenomenon exists.

Remember too that many of the clinical features attributed to androgen deficiency may instead be caused by E2 deficiency leading to reduced ER signalling. So one of the most important things about still having T while on bicalutamide is that it is readily available for conversion to estrogen.

This is why I think low-dose transdermal estrogen should be SOC for men on ADT. It makes no sense to me whatsoever to deprive a man of all his T-derived estrogen and not replace some of it.

ragnar2020
ragnar2020 in reply to noahware

Hi Noahware,

Glad to hear your results the other day, and happy that you've entered this string of commentary about ADT. ADT use is a very complicated chemical puzzle that guys with PCa are suddenly tossed into the middle of and expected to learn. Richard W has written a whole book about how to navigate the damn SEs.

Jeff

noahware
noahware in reply to ragnar2020

Thanks. Sadly, I think it may take decades (if ever) for tE2 to become mainstream in the US, even if PATCH trials and further studies show it to be a safer form of ADT.

In the meantime, I think we should all be mentioning to our docs and to each other that low-dose tE2 makes sense for guys on standard ADT. I have yet to see what I consider a good argument for NOT using it.

RSH1
RSH1 in reply to noahware

I asked FOUR different SOC doctors about estrogen patches for ADT. Responses:

1. Yelling and telling me I was going to hurt myself. (that was from Mayo)

2. It doesn't work. No reason to discuss. (another doctor at Mayo)

3. It doesn't work. When pressed that doctor finally admitted that he didn't know much about it since he was trained in the 90's.

4. It works but not as well as Lupron. The only reason it was used in the 40s-80s was because it was the only thing that they had and it was better than nothing.

I did it anyway, and it worked. T went to undetectable levels. I have a good relationship with doctor#4. She's smart and logical and after the Estrogen/Lupron thing tends to let me do what I want and just gives me info/suggestions.

MateoBeach
MateoBeach in reply to noahware

Completely agree. More need to request and try it. So much better!

George71
George71 in reply to ragnar2020

ragnar,

I agree with your comments completely -- and as I described in my above comments,

(and noahware seems to agree ? ) the bicalutamide would have to be magic to only block A/R on PCa cells -- if that were the case your blood levels of T would not be doubling.

A/R receptors are all over your body ... -- the brain is full of them, virtually every muscle etc. that is why men develop muscles better -- muscles drink up testosterone.

the prostate only uses a small amount of T --- muscles are every where and they all have A/R and receive the same hormone -- testosterone . Anything that blocks the A/R that travels in the blood stream blocks A/R anywhere it finds them.

No doubt bicalutamide can't block them all --all the time -- and is therefore less effective and less side effects -- but it is still a formidable ADT that deserves respect -- it will lead to the same end if continued long enough. It's not like being OFF ADT as LearnAll seems to think.. nor is it only depriving prostate and PCa cells.

MateoBeach
MateoBeach in reply to noahware

Good analysis. I agree and found that adding estradiol topical to ADT made life and side effects SO much better for me. No libido but clear cognition, better energy, no hot flashes and happy.

Mamatal57
Mamatal57 in reply to LearnAll

What fraction of Pca people is bicalutamide specifically suitable for?

LearnAll
LearnAll in reply to Mamatal57

It depends on many factors and taking a composite view of various characteristics of some ones prostate cancer. No body is interested in bicalutamide after 2013-2014 when Abiraterone and Newer lutamides start coming in market. Unless we try bicalutamide, we will not know with certainty if we are good responders or not. In my case, bicalutamide caused almost 86% decrease in PSA in 30 days. (from 830 to 114.) so I am a believer in old, inexpensive bicalutamide.

I have been on Lupron solid for almost 4 years, wondering if Im a candidate for the bical?

Survivor,

I was on lupron for 9 months and felt that it was corroding my body and mind. When my Nadir PSA reached 0.2 ...I decided against the opinion of my onco. and went on off period of ADT...After off of all ADT for 8 months, my PSA started going up and reached 2.1 . Then, I started on Bicalutamide 100 mg /day and Finasteride 5 mg a day and Tamoxyfen 10 mg a day . I got my labs today. In last 40 days ,My PSA has gone down from 2.1 to 0.6 ( 71% decline) and ALP has gone down from 70 to 60 ( 15% decline) . I have decided to continue the above 3 meds along with my heavy plant-based diet and 5 miles a day walk as long as this combo works. My MRI 2 weeks ago shows no lesion bigger than 4 mm and that only 2 or 3 faded ones.

I can not give you advice..I can only report my experience with the above combo which has almost no side effects for me.

So cool tht you are right on top of your treatment. Its impressive. Ive been just rolling with what my Onc, Mayo Phx, tells me. Maybe not good, especially since I read below that the docs have outside influences on which meds I get.

George71
George71 in reply to LearnAll

Thats a great report LearnAll -- congrads

LearnAll
LearnAll in reply to George71

Thanks George...Every one in my family and my primary care doc are excited now. They were worried when I decided to not go on lupron or Zytiga and chose Bicalutamide and Finasteride based on Dana Farber study I quoted above. Believe me ..the side effects are minimal. I have been on these for last 6 weeks. Energy better, no hot flashes, sex life getting better and mood better with much less forgetfulness. I am praying to God to let me have at least 3 years on Bicalutamide and Finasteride.

Hi Survivor1965,

Here is something to think about --- since you are 4 years on lupron and not CRPC with apparently very low PSA and holding --super high testosterone supplementing isn't really much different at all from doctors who frequently take patients off ADT for an "OFF period" to see if their PSA starts rising and at what rate (doubling time) etc,

They do this because of the many possible co-morbidity issues that come with long term ADT.

Casodex is a milder option but still a form of ADT. If you choose to continue with an ADT -- I think Casodex would be a better option because it is milder.... but if you choose to get a true "OFF period" and stop all ADT -- then you may consider taking super high testosterone -- rather than waiting for the testosterone to slowly return like is usually done-- I think they are finding out they have many more relapses by just letting T come back slowly ....

When you stop the ADT (whatever form you are taking) and immediately start continuous super high testosterone it shocks the PCa cells to death and plugs up any remaining -- where they cannot function (they have to expel the T from the cell to start the next splitting cycle) -- and they can't because they are constantly bloated with Super levels of T . some men are on continuous super high testosterone and nothing else -- for many years.

Hi G,

My Docs tell me I am castrate resistant because I have failed Lupron with Zytiga even though Im on Lupron with xtandi now.

I have discussed taking a break from ADT and my onc, Dr Bryce Mayo Phx, told me I would be dead in 12 months, with the final few months in sheer hell.

I have heard of the high level testosterone treatments. I will ask my care team. I appreciate you help, its hard to follow all the jargon and advancemnts on this site. I feel like Im not able to follow along anymore.

They are not equally effective.

LearnAll
LearnAll in reply to Tall_Allen

Yes. In most patients, bicalutamide monotherapy is LESS effective than Lupron. Only in a small subset of patients, bicalutamide can be nearly as effective as lupron....Therefore bicalutamide alone can not replace lupron in majority of advanced cases.

Tall_Allen
Tall_Allen in reply to LearnAll

Where is this subset you speak of? How are you evaluating effectiveness? I am using radiographic progression, which is the only recognized surrogate endpoint.

LearnAll
LearnAll in reply to Tall_Allen

Dana farber study which I mentioned above made the conclusion that bicalutamide plus Finasteride is equal in efficacy to lupron. The link may not be working but if you go to pubmed you will find this study.

pubmed.ncbi.nih.gov/15151957/

By M H Tay, D S Kaufman et al.

George71
George71 in reply to LearnAll

LearnAll

the broader point to all this is:

"No doubt bicalutamide can't block them all --all the time -- and is therefore less effective and less side effects -- but it is still a formidable ADT that deserves respect -- it will lead to the same end if continued long enough. It's not like being OFF ADT as LearnAll seems to think.. nor is it only depriving prostate and PCa cells."

Tall_Allen
Tall_Allen in reply to George71

"it will lead to the same end if continued long enough." Demonstrably untrue.

Tall_Allen
Tall_Allen in reply to LearnAll

I guess you don't understand what radiographic progression means. It means progression that shows up as increased size and number of metastases. Since that 2004 study, we have learned that PSA alone is not a good measure of progression.

LearnAll
LearnAll in reply to Tall_Allen

Nobody said PSA alone is enough to measure progression.

Tall_Allen
Tall_Allen in reply to LearnAll

Yet that is exactly what they did in the reference you cited.

Tall_Allen
Tall_Allen in reply to LearnAll

BTW- I do not believe that any of the doctors who did that 2004 study still practice that. We've learned a lot since then. Time to get unstuck from the past.

LearnAll
LearnAll in reply to Tall_Allen

The "forum doctors" like you also will not be practicing some day...does that mean the knowledge you left suddenly became wrong. Your negativity and fearmongering is an old habit. And the distortion you do to other peoples statements are unbelievable. I am not getting in arguments with any pseudo doctor.. Bye.

maley2711
maley2711 in reply to LearnAll

How do we average guys here determine which participants are " doctors" and which are pseudo-doctors? Of those who are contributing here, few including any study links for most of their assertions.....thus we average guys are left to scratch our heads? Comments such as " it would just make sense" do not indicate a scientific approach to reaching a conclusion.

LearnAll
LearnAll in reply to maley2711

That is a problem in such forums that because one can not tell his/her educational qualifications and experience so members can not get an idea of credibility of some ones assertions. Even if we knew, in a system which puts profit at the top, there are competing vested interests who contaminate the knowledge thrown here. e'g' a person who is paid commission by a drug company for advertising a certain new drug or treatment can hide behind a false name and incessantly sing the new medication's praise songs and demonize older, cheaper meds/treatments. Or may be a person is advertising a certain clinical trial. We can not know.

But still such forums are wonderful places because we get opinions and ideas of all shades and colors ..letting us think outside the SOC box and choose wisely what is the best path for us. I do not believe anyone willfully misleads us here but sometimes out of ignorance, a fact can be presented in wrong way. We have to check and verify from multiple sources if a certain information is right or wrong. Also it may be right for one man but wrong for another. We are all unique human beings.

George71
George71 in reply to maley2711

maley2711

to answer your question, No one on here is a doctor in any medical field pertinent to prostate cancer -- .. There maybe one that "plays doctor" on here --- I call it a "wanabe doctor" - who masquerades as if an authority. Once he weighs in on an issue he states his opinion in a manner that makes clear -- all other views are ... in his words "absurd" / "uninformed" / "ignorant" / "knowingly and willfully misleading" /" lying" / .. "don't ask for other opinions because he has already told you" etc etc.. often talks down to others rather than voice his opinion and allow others to voice theirs.

For example -- he said that Dr. Kwon and Mayo Clinic are willfully and knowingly misleading people with their video conference info. He claimed the world famous Mayo Clinic is weak in oncology --he said they use second rate imaging pet scanner C-11 and he discredited Dr. Kwon achievements and views by saying he not a medical oncologist just a Dr. in urology-- and the irony of that statement is -- the person saying that -- -- doesn't have a medical degree in anything.. he is just a blogger on forums like the rest of us.

here is the doctor:

youtube.com/watch?v=60P98QL...

WSOPeddie
WSOPeddie in reply to George71

He has also condemned HIFU and gone as far as labeling HIFU surgeons as greedy "car salesman" types in the business of ripping off their customers. He is certainly arrogant enough to be a doctor.

maley2711
maley2711 in reply to George71

THANKS for the informative video.....though some of the info was indeed disheartening...specifically PSA = 0 and metastases!

George71
George71 in reply to maley2711

That is because the patient is on ADT and it artificially makes your PSA almost 0 -- 0.03 and stuff like that -- that is the problem with ADT -- it kills a small amount of the low grade cancer cells and therefore shrinks the cancer down but the hard to kill cells remain and mutate into much more aggressive cancer it takes a few years but it is likely to come roaring back -- and these cells are CRPC... it seems to me -- while you are still not CRPC -- you should try and kill off all they can find and then go for super high testosterone -- it kills cancer cells (makes double strand breaks in PCa cells) any surviving PCa cells are bloated and become dormant sometimes for years. You will never become CRPC this way and that is the biggest threat to our lives -- try and avoid CRPC if possible -- that is not to say that even then as the video shows he can beat it down and overcome it at any stage ... just is a lot harder...

George71
George71 in reply to LearnAll

LearnAll,

There you go again misleading the group... Tall Allen is not a doctor in any medical field -- please don't confuse me by calling him a "forum doctor".

LearnAll
LearnAll in reply to George71

Chill George. You need to understand "sarcasm" ...take it easy.. peace of mind helps us fight cancer cells better.

maley2711
maley2711 in reply to Tall_Allen

Allen -

Do you have any problem with Dr. Kwon's approach with some of his cases?

Tall_Allen
Tall_Allen in reply to maley2711

I have a problem with that video, which is misleading to patients.

maley2711
maley2711 in reply to Tall_Allen

Thanks! In general, for those who might be misled, in what way misleading?

Tall_Allen
Tall_Allen in reply to maley2711

Explained here:

prostatecancer.news/2017/05...

maley2711
maley2711 in reply to Tall_Allen

Thanks Allen. Unfortunately, that page no longer exists...at least using my computer?

I will guess the blog discusses the need for randomized studies? Or another angle?

Do you completely discount Kwon's approach?

Tall_Allen
Tall_Allen in reply to maley2711

The link works fine for me. Try this one:

pcnrv.blogspot.com//2017/05...

maley2711
maley2711 in reply to Tall_Allen

Ok...Thanks. that worked. It seems that you are saying that it will be difficult to have conclusive results from randomized testing, that you are skeptical about the efficacy, and that once there is metastasis, any treatment should be considered only for palliative purposes. Aren't something like 70% of PSA recurrences after primary treatment indicative of non-local metastases? So ADT should only be done for palliative purposes? Easy to get lost in the weeds on this stuff!! Allen, do you have a scientific background?

Tall_Allen
Tall_Allen in reply to maley2711

I am saying that it is impossible to make any conclusions about metastasis-directed therapy without randomized testing. As far as we know, it is only palliative, but perhaps randomized testing will show that there is some benefit.

Recurrences after primary therapy may be local, locoregional, or distant. ADT and radiation may slow progression or even cure if the recurrence is local or locoregional only. When there are distant metastases, we know that ADT extends life. We don't know if there is a benefit to treating metastases.

Yes, I have a degree in biochemistry and am well-versed in statistics and research from 20 years on the job.

maley2711
maley2711 in reply to Tall_Allen

Thanks Allen..not sure everyone here has an understanding of your background. Makes me feel a little better about my ignorance of much of what is discussed here....... no biochem background!! A little late to start now!! As for your wrapup above...pretty much in alignment what my Uro stated some time ago......" Dale, we still have many more questions than answers! "

Tall_Allen
Tall_Allen in reply to maley2711

What got me into this was my ability to translate from Medicalese to common English. The men in my live support groups felt that I explained things more clearly than their doctors, so I started going with them on their visits. Their doctors loved me too because they could talk to me in Medicalese. It helps to be bilingual ;-)

maley2711
maley2711 in reply to Tall_Allen

Thanks Allen ! You sound like a great guy! It's unfortunate that once in a while your intent is misinterpreted, and might be interpreted as belittling another participant......some folks are more sensitive than others . I have been accused of being overly sensitive! Guess it never hurts to reread what we have written and check for possible misinterpretation...... I've learned that lesson from having some of my email messsages interpreted differently than I intended! Hopefully some other guys are reading your replies to me and now better understand your background and why it gives us good reason to strongly consider your input!!! Plaudits to you for going above and beyond in helping others.....both here and with guys in that live support group!

I see I should have read further, I think this answers my question on switching from Lupron.

It seems that Bicalutamide is equally effective for M0 patients but not for M1 patients:

M0: pubmed.ncbi.nlm.nih.gov/110...

M1: pubmed.ncbi.nlm.nih.gov/964...

noahware
noahware in reply to GP24

I can't put my hand on the citation at this moment, but I read that for the 1998 Tyrell study, a sub-analysis of the M1 men found the disadvantage existed only in men with PSA > 400. For the M1 men with PSA <400, the bicalutamide was not found to be inferior. So that remains a bit controversial to me, but that is the study that has resulted (at least in the US) in avoiding 150mg monotherapy for M1 men altogether.... not that it's done much in the US for M0 men, either.

This is an example of a common theme I've seen in the literature:

"CONCLUSION: Bicalutamide monotherapy yielded comparable results relative to standard treatment with MAB, induced fewer side effects, and produced a better QOL."

George71
George71 in reply to noahware

As Ragnar2020 said:

"Several guys on this forum are using tE2 for their ADT. But since the use of tE2 is not endorsed by MOs who follow the NCCN SOC guidelines for ADT drugs, the use of tE2 is occurring in the UK, Canada, Aust, and the EU, but it is no longer available in the US. The SEs of tE2 are supposedly less than with SOC ADT drugs, but that'll be something I hope will be elaborated upon here."

I can't agree more -- tE2 is likely the safest and best form of ADT you can do. But of course -- there is a lot more money in lupron .. I was told the doctors cut for giving each shot is $600 -- get about 50 patients on lupron shot monthly --- thats pretty sweet.

Same with Bicalutamide -- works very well costs one tenth as much -- off patent --

Actually Bicalutamide may work better-- when all things are considered .. because it isn't able to block off all testosterone everywhere -- people may last longerbefore becoming CRPC ...

Which takes me to -- with a slow enough doubling time -- and very conservative limiting damage treatment without ADT to avoid CRPC -- even if it is advanced and progressing -- you will live a long healthy life ... and out live it... Many have. With all the dibilitating treatments the OS is only extended a year or so -- if that. And in many cases the treatment kills you.

Tall_Allen
Tall_Allen in reply to George71

This is only if you use PSA as your measure of progression. What we learned from STAMPEDE and similar RCTs is that two therapies can reduce PSA to undetectable levels, but the stronger one prevents new metastases, extends survival, and delays time to castration resistance (the opposite of your unsupported claim).

Bicalutamide as monotherapy for mHSPC is a relic of the past.

George71
George71 in reply to Tall_Allen

"Bicalutamide as monotherapy for mHSPC is a relic of the past."

I agree wit that -- as is (in my opinion) All ADT as a "monotherapy" they need to be putting something with it.. Immuno -- radiation, surgery ...

Tall_Allen
Tall_Allen in reply to George71

What I meant is that the only use of bicalutamide in metastatic men is to initially prevent the testosterone flare of subsequent ADT. Other than that, bicalutamide has no use at all in metastatic men.

GP24
GP24 in reply to Tall_Allen

On the other hand, Traveller is quite satisfied with his Bicalutamide monotherapy.

healthunlocked.com/advanced......

Tall_Allen
Tall_Allen in reply to GP24

He has not been diagnosed with metastases, to my knowledge.

GP24
GP24 in reply to Tall_Allen

Yes, I would not recommend Bicalutamide for M1 situations. However, there is always an exception. I know a patient over 90 years old with bone mets and severe cardiovascular problems. He takes Bicalutamide.

LearnAll
LearnAll in reply to GP24

Not just traveller....Magnus was on casodex monotherapy for 5 1/2 years. and other fellow member, Coastguy is doing well on bicalutamide. There are men with bone mets for whom bicalutamide has worked for years but its not possible to find out in advance who will do well and who will not do well on it.

Last month I reported on this forum a case from Japan who was on bicalutamide for 4 yrs and when it was stopped his PSA remained undetectable for next 8 years.

Tall_Allen
Tall_Allen in reply to LearnAll

How do you know any of them are "doing well"? You have no idea how much better they would have done with SOC therapy. This is the kind of comment that harms patients. The only way to know such a thing is with a randomized clinical trial. Use science, instead of shooting from the hip.

Hi Tall Allen,

I place a lot of faith in the personal experiences and information offered by the guys on this and other forums. I’ve observed that you do not seem to value these observations much and actually seem hostile to anything that deviates from the NCCN SOC. I value your opinions, but I value the experiences of others equally.

Jeff

Jeff,

If there is any hope of living longer with PCa and maintaing QOL, it is through science. Being human, and thus subject to a kind of cognitive error called the "availability heuristic," we have a natural tendency to overvalue anecdotes and undervalue statistics. Remember that in a trial of 1000 patients, each one has a story to tell- even if their stories are not on this forum. So ask yourself why you value anecdotes as much as research - I think you may change your attitude if you do.

I am only hostile to those who willfully harm others. Ignorance of what the latest trials are telling us, of research methods, and statistics is certainly understandable in patients uneducated in those arcane disciplines. Those who exhibit confirmation bias, or hide their heads in the sand are less understandable. Even so, if they just want to harm themselves, that is their lookout. However, those who refuse to stop misinforming others are guilty of an unconscionable sin.

LearnAll
LearnAll in reply to Tall_Allen

TA ...you need to shed your false belief that there are forum members who are willfully trying to harm patients. That is simply not true. Every one is trying to contribute what they think and what they read so a meaningful discussion can occur.

Most people here are 50+ years old grown up adults who s till have their logical mind to sort things out themselves. Your hostility and attacks gives the impression that people on the forum are some lost sheeps who you have to shepherd otherwise they all will lose their way.

Also, new drugs are not always better than old. But that's what sellers want people to believe. If new drugs were all better...we will not have Zytiga causing high blood pressure, high blood sugar, atrial fibrillation and increased rate of heart attacks. Similarly, Extandi may not be causing seizures while driving killing the patients and innocent other people on road. Lot of times, Old Is Gold and bicalutamide is that old beauty who is still attractive and useful than some dangerous new drugs being pushed on people.

Tall_Allen
Tall_Allen in reply to LearnAll

It is not a false belief that your posts are based on willful ignorance. Ignorance is forgiveable, but to consciously misinform others is not. How else would you explain your recommendations to patients that hark back 20 years or more and that you continue to make after you have been shown they are demonstrably false.

Statements like: "Lot of times, Old Is Gold and bicalutamide is that old beauty who is still attractive and useful than some dangerous new drugs being pushed on people." are a good example of the fake news that you continue to post after I have repeatedly shown you it is false. Why would you do such a thing?

gregg57
gregg57 in reply to Tall_Allen

When proving a point becomes most important thing, the truth becomes subservient to that purpose.

George71
George71 in reply to Tall_Allen

T/A ,

You should try listening to what ragnar2020 and LearnAll are trying to tell you for a minute.. they said it very well --and they said it with respect for you as a person even while you are accusing them and others of deliberately misleading people on the forum... ... no one but a fool would come here and try and mislead others -- we are sharing our real life experiences -- what doctors have told us ...etc etc and looking for better than SOC -- it is sadly lacking . If it was all that great we would all be doing it. Our doctors have already told us what SOC is if that is all you have to offer. I have personally seen more that 20 doctors (specialists in this field) and they all have a different opinion ... how could you of all people ( not a doctor in any medical field) come on here and be an all knowing authority -- accusing actual doctors of knowingly lying -- I for one don't need you to protect me from Dr Kwon and Mayo Clinic or Dr. Morgantaler etc .. They aren't lying either in spite of what you said. We all have doctors we listen to... we are all on treatments of some kind -- and we are all doing our own research -- i'm picking up really good ideas all the time ... These guys have some really good ideas and i for one want to hear all of them including the ones I may disagree with -- I can change my mind too.... I need to hear their logic -- I may try their approach! We are searching for better.. we know what SOC does -- after all the years of damaging co-morbidity cycles you may gain a year or so at best -- if you don't die from the treatment first --- LearnAll just told us of a man that is 8 years out after 4 years on bicalutamide and you accuse him of lying. How does that help the forum community?

Tall_Allen
Tall_Allen in reply to George71

I did not accuse ragnar2000 of any such thing, only LearnAll. I think you should be careful about the advice you receive. Apparently, you need help with this stuff, or you wouldn't be asking questions on this site. I said nothing about Morgentaler. These are strawman arguments. Anecdotes aren't science. I don't expect you to understand what science is, but I do expect that people will not intentionally disregard science.

LearnAll
LearnAll in reply to Tall_Allen

"why would you do such thing/" I am asking you. Stop accusing people...drop your paranoia...allen(the know it all) . I strongly object your utterings that I am consciously misinforming people. I shared my experience with bicalutamide and wanted fellow members to know that this med dropped my PSA 86% in 30 days and that,s why I call bicalutamide "old is Gold" and "old beauty" For me it is...as second time once again it lowered my PSA 76% in 40 days which is still falling ....bone specific ALP all the way down to 10 with minimal side effects. If you keep insulting me.. I am warning you that you will receive counter-attacks in your kind of words and in your language.. So cease and desist !

Tall_Allen
Tall_Allen in reply to LearnAll

I understand that you believe your anecdote proves something - it doesn't. Biomarkers are not cancer. When STAMPEDE proved that heavier treatment extends life over lighter treatment, they used radiographic progression and survival to prove it. Learn some science.

LearnAll
LearnAll in reply to Tall_Allen

"learn some science" You said.

No wonder people say to you " we do not need another daddy."

ctarleton
ctarleton in reply to LearnAll

By this time, both Zytiga and Xtandi are no longer particularly "new" drugs, much less being "pushed on people". They both went through rigorous Phase I/II/III Clinical Trials, where extensive statistical evidence (not just anecdotal reports) was collected, analyzed, and presented to bodies such as the US FDA, which resulted in rational, fact-based Approvals of these drugs for the proper Indications. It is not a matter of anyone's belief, nor wishful thinking, nor a questionable hope that some outdated treatment or unproven "alternative" may be somehow better, etc. despite the lack of rigorous comparable evidence.

gregg57
gregg57 in reply to ctarleton

Keep in mind that you are talking to someone who said:

This is our SOC so anyway we will put you on these meds..whether you need or not. We don't care even if you have a very slow growing mildly metastatic case...We decided that it is SOC so its our drug Hitler's order that you will have to take it. Don't even ask if I really need it? Its our SOC order ! Period.

I point this out not to be critical, but rather to explain how bias can influence the content presented and cause a loss of objectivity. When such a level of bias is presented, it requires us to scrutinize the content and watch out for invented "facts" used in service to further the writer's agenda.

noahware
noahware in reply to Tall_Allen

"Remember that in a trial of 1000 patients, each one has a story to tell- even if their stories are not on this forum. "

But what you seem to miss is that their individual stories are not really in the STATISTICS, either. What is in the statistics is 1000 heterogeneous stories put in a blender and homogenized, then divided by 1000, and translated into one homogeneous and oversimplified story that is a PARTIAL representation of a more complex reality.

"those who refuse to stop misinforming others are guilty of an unconscionable sin"

Well of course you think that, as a high priest in the Church of Statistical Significance. Those who stray from the Church and refuse to follow, worship and praise what the stats dictate are ALL sinners. That of course includes not only many men who post here but many thousands of doctors and researchers who dare say something like "iADT is not clearly inferior, and might even be better for SOME men... it's not conclusive."

OF COURSE it is conclusive, you will counter... the STATS say so. And the stats are the Word of God. Anything not in the Bible of Statistical Significance is "misinformation" because there is no such thing as TRUE information unless it flowed from a clinical trial.

This is your real message to men with PC: ignore the fact that you are a unique individual who will quite possibly respond BETTER than average or WORSE than average to any given protocol and pretend instead that you are not an individual at all, but that you are the "uber-average" 1/1000 of a thousand men OTHER than you that got put into the blender that is the Church of Statistical Significance. Your actual entire story doesn't matter, just as the individual stories of those 1000 men don't matter in their full and complex detail, because all that matters is the single simplistic mega-story distilled from the aggregation and statistical analysis of 1000 small slices of the stories of real people.

George71
George71 in reply to noahware

noahware,

And might I add , that SOC is lagging 10 years behind the technology --as well as the clinical and observational findings, which are leading to innovative combinations of treatments occuring as we speak-- the fact that ADT is now been backed down after 20 years of SOC should tell the SOC only folks something.... nevertheless the advocate for SOC and strictly SOC doctors will be the last to be able to take advantage of any of it (ten years later when the double blind trail results are published)

SOC doctors will never discover anything new -- will never try anything new -- and will never be able to use the up to date innovative techniques years ahead of its time because by definition they are strictly SOC.

noahware
noahware in reply to George71

Note too where much new research and clinical trial money flows: to find new drugs to extend life after the FAILURE of SOC drugs. It is all about finding new and expensive ways to treat castrate RESISTANT men, who have seen SOC possibly help to render their disease less responsive to further treatment. Where is the money for researching any basic change in initial SOC, which is assured to fail?

George71
George71 in reply to noahware

noahware,

There you go again, thinking for yourself and making too much sense.

To qualify as a new therapy drug with the FDA you merely have to equal ("be as good as" -- to be an approved alternative) or exceed standard of care by merely 10%. then you can sell it for $20,000 / $30,000 per treatment.

Of course you must pay for their previous drug @ $20,000 and fail before you qualify for the "better one". Otherwise if they gave you the better drug , you would stop buying their "SOC" one.

What seems to have occurred with the drug companies is they have had blinders on trying to make 4 or 5 more versions of ADT over the past 15 years or so to sell us for $1000 a pill .. And, now that they have succeeded in cutting off every drop of T and getting our PSA to 0.000001 -for a couple of years, more people than ever before are turning up nmCRPC .. a relatively new condition... possibly caused by or sped up by their new super cool ADT . Now they get to treat us with another drug they are developing for treating the CRPC they may have caused.

Tall_Allen
Tall_Allen in reply to noahware

Perhaps you don't understand how randomized clinical trials are done. Randomization assures that both groups are identical, and the clinical trial specs guarantee that they are all treated exactly the same way. The statistics have some powerful properties. Among them is the bell shaped distribution of outcomes with the mean at the center. This means that 95% of patients will fall within 2 std deviations of the mean. Anyone who would bet on a different outcome will lose his money. Because the stakes here are high, one is betting with his life.

I am amused that you seem to know how I will answer your questions. I guess we can just listen to your ravings rather than asking me.

noahware
noahware in reply to Tall_Allen

"Randomization assures that both groups are identical"

Identical? You said that in a trial of 1000 patients, each one has a story to tell. Are they identical stories? All that randomization "assures" us of is that, with increasing numbers, unseen differences that do exist are less likely to matter and that the two groups become CLOSER to being identical. That is different than BEING identical.

Take a group of fifty men and randomize them, and then tell me that the 25 and 25 in each group are "identical" in terms of things like having strong belief in the treatment, will to live, etc., let alone in terms of all genetic and physiological differences. If one could even measure these things, it is highly unlikely that a random distribution in a small group would end up being a 50-50 distribution.

The fact is, heterogeneity of men in general and of PC in particular assures as that any two groups of men will NOT truly be "identical" except in the terms dictated by the parameters of the study.

"Anyone who would bet on a different outcome will lose his money. "

Okay, bring your money and let's roll dice. Statistics tell us a seven is most likely to be rolled. You bet on a "seven" and I will "bet on a different outcome" and we will see who will lose his money.

Aggregate betting results, for statistical outcomes over thousands of events, is not the same as betting on individual events. I'll "bet" there are doctors who could assess the OVERALL health and disposition of certain patients and win by betting AGAINST the numbers (and take YOUR money), because they understand that men can be far more than their PSA scores or their PC scans, and these doctors make their bets by assessing other medical factors as well as intangibles like "the spirit" of the patients.

The reality of trial of 1000 patients, each one with a story to tell, is 1000 anecdotes that fall into three basic outcome categories: as statistically expected, better than expected, and worse than expected. Yes, a small statistical benefit in median overall survival PROBABLY means that one treatment can benefit more men, more greatly, over the short to intermediate term. But these survival benefits do not always hold over the long term, and they may come at other costs that men as individuals do not subjectively value as worth incurring for the potential benefit.

George71
George71 in reply to noahware

Yah, and it seems we are often being given false choices by the drug industry .

They run a trial -- against 2 minimally effective drugs like for example injecting their patented version of what maybe basically bleach for all we know vs drinking a mild acid -- and after 5 years conclude that one lowered PSA 10 percent more than the other. Nevermind the PSA shoots right back up 2 months later..

The drug companies will never fund a trial comparing super high testosterone with lupron ...@ bio-chemical failure ... there is no money in that .. .. but if they had a drug that showed anywhere near what observational / clinical studies are showing with testosterone -- it would be front page news.

Tall_Allen
Tall_Allen in reply to noahware

They are identical as a group. You should read about the normal distribution and its properties.

maley2711
maley2711 in reply to Tall_Allen

Thank you Allen...anecdotes are not science.

noahware
noahware in reply to Tall_Allen

" What we learned from STAMPEDE and similar RCTs is that two therapies can reduce PSA to undetectable levels, but the stronger one prevents new metastases, extends survival, and delays time to castration resistance."

Can you provide an actual reference to the individual studies showing reduced overall survival for bicalutamide?

Tall_Allen
Tall_Allen in reply to noahware

That was established in the last century with randomized clinical trials such as this:

karger.com/Article/Abstract...

As you can see, bicalutamide monotherapy reduced survival relative to castration by 30%. It is difficult to understand why anyone in this century would advocate such a thing.

noahware
noahware in reply to Tall_Allen

I thought after your comment about "old studies" you might have something more recent, as you mentioned STAMPEDE, etc.

As I mentioned in another post on Tyrell 1998, a sub-analysis of the M1 men found the disadvantage existed only in men with PSA > 400. For the M1 men with PSA <400, the bicalutamide was not found to be inferior, with results the same as for M0 men.

So that seems to be the only study that has resulted (at least in the US) in avoiding 150mg monotherapy for M1 men altogether.... not that it's done much in the US for M0 men, either.

We see that "At a median follow-up [of] 100 weeks ‘Casodex’ 150 mg was found to be less effective than castration in patients with metastatic disease (M1)... with a difference in median survival of 6 weeks." So the lesson is, if you plan on dying soon, this is not the drug to extend your life but it MIGHT be the drug if you want that shortened life to be better, since we also see that "in symptomatic M1 patients, ‘Casodex’ was associated with a statistically significant improvement in subjective response (70%) compared with castration (58%) and [improved] quality-of-life.

But since you have already decided that LENGTH of life is objectively better the QUALITY of life for ALL men (regardless of their own opinion) you don't bother mentioning that, and we hear from you that bicalutimide 150mg is a "useless" therapy.

What about those who DON'T die within the first two years of their chosen therapy? "A further survival analysis in patients with M₀ disease is therefore planned when the data are more mature." Where is that data?

Since that study over two decades ago, this is an example of a common theme I've seen in the literature: "CONCLUSION: Bicalutamide monotherapy yielded comparable results relative to standard treatment with MAB, induced fewer side effects, and produced a better QOL."

Please don't cherry-pick SINGLE studies to support your points (as with the Hussain study on iADT) when there also exist other studies that do not reach the same conclusions. So how about mentioning some besides Tyrell 1998 that might show inferior OS over a more meaningful time span?

Tall_Allen
Tall_Allen in reply to noahware

There wouldn't be anything more recent because we have moved on. Bicalutamide monotherapy is very seldom used anymore for metastatic men. Why would anyone want a worse treatment if they could get a better treatment?

You mistake inconclusive results from lack of sample size for lack of benefit. That's why subgroup analysis is always suspicious. You can't make a silk purse out of a sow's ear. There were several other randomized clinical trials but none recently because that would be unethical now that we know better.

I don't argue against use of bicalutamide in non-metastatic men, only in men with metastases.

Large Phase 3 randomized clinical trials are precious. They are not "cherry picked," they are practice-changing. It's bad for your health to discount them.

noahware
noahware in reply to Tall_Allen

"Why would anyone want a worse treatment if they could get a better treatment?"

There you go again, defining subjective terms like "worse" and "better" for all men, instead of letting them decide for themselves.

If we had you as a benevolent dictator, the hypothetical question of "would you prefer to live your last 100 weeks under house arrest before execution, or to be executed at 94 weeks but have more freedom until then?" would never be asked, because the extra six weeks of life would be DEFINED as "better" independent of individual preference!

Tall_Allen
Tall_Allen in reply to noahware

Treatments that extend life more, and treatments that extend time to castration resistance more are objectively better than treatments that do not. This is science. What's more, QOL is also improved in the long run. It is important to judge QOL on the basis of the entire life (researchers measure this in "quality of life years") and not just the first few months. A man can feel better with no treatment whatsoever right now, but will deteriorate rapidly as metastases grow and body systems begin to break down. Unfortunately, this is what happens with metastatic cancer. Your myopia is harmful to your health.

noahware
noahware in reply to Tall_Allen

"Treatments that extend life more, and treatments that extend time to castration resistance more are objectively better than treatments that do not."

They are "objectively better" ONLY when judged in the context of the pre-defined scientific parameters. By this type of definition, it would be "objectively better" to never get in a plane, train or automobile because by doing so one would reduce his risks of death by plane, train or automobile travel.

Marginal risk reduction, with an intent or marginal life extension, is not the solitary consideration of medical intervention from the individual PATIENT perspective, even if it is from the scientists' perspective. You want to define things as if men are your science projects. But men have different reasons for choosing different treatments, especially if they know the treatments are ONLY delaying tactics that do not offer cure.

Here's what we know about the "better" treatments: your body STILL will deteriorate rapidly as metastases grow and body systems begin to break down, anyway.

"researchers measure this in quality of life years"

No, they don't. What cannot be measured cannot be measured. They PRETEND to measure it.

Tall_Allen
Tall_Allen in reply to noahware

I agree that to some mentally defective people (i.e., those suffering from intractable depression) that given the same reasonably good QOL, living less may be preferable to living more, and to a masochist, living without suffering may be less preferable than living with suffering. What color is the sky on your planet?

noahware
noahware in reply to Tall_Allen

" What color is the sky on your planet?"

Why would you care? You have already decided the sky for "men" as an aggregate is more important than the sky of any individual, since "the same reasonably good QOL" is NOT what each and every individual experiences under different treatment regimes. But who cares, anyway? They are just "anecdotes."

Next thing, so far as sky goes, you will be telling us seven straight days of cool, gray weather is "objectively better" than four days of warm sunshine followed by three days of sleet.

"living without suffering"

... is not possible, nor something anyone on this forum would think was possible.

PS - I love that people with intractable depression are "mentally defective" in your words. Perhaps a certain politician can use that in an upcoming debate.

Tall_Allen
Tall_Allen in reply to noahware

DSM IV defines mental defects. Intractable depression is a mental defect just as cancer is a physical defect.

I hope your crystal ball about your individual prediction is right. Perhaps you should add a few voodoo incantations. Abandoning science is dangerous to one's health.

noahware
noahware in reply to Tall_Allen

My understanding of "mentally defective" is the legal definition, as one who poses a danger to himself or others or cannot manage his own affairs. Perhaps that could include some depressed people, but it actually sounds a lot like a label you might put on any patient (or doctor!) who opts for any path forward other than the one dictated by the Church of Statistical Significance.

"your individual prediction"

I have made no predictions. Predicting what is unknowable is YOUR business, not mine.

"Abandoning science "

"Abandoning science" is exactly what people do when they suppose they can objectively measure that which is subjective and not measurable.

noahware
noahware in reply to Tall_Allen

BTW, there is not anything like "Casodex For Life" being considered by any of the men who might start with that drug. It is an entry point to definitive systemic therapy. I haven't yet bothered to ask, but: what studies can your refer me to that would indicate a year or two of bicalutamide would definitively or severely impact the efficacy of potential future treatments like chemo, radiation, standard ADT, high-dose T, high dose E2, etc.?

Tall_Allen
Tall_Allen in reply to noahware

Your lack of understanding of the the natural history of cancer is apparent. "Just a year or two" is a scary statement. In "just a year or two" millions of cancer cells are at work, replicating and preparing the soil for more tumors. What the rest of us have learned about early treatment is that "just a year or two" makes all the difference in survival and castration resistance. Read the STAMPEDE trials until it sinks in.

noahware
noahware in reply to Tall_Allen

Yes, because as we all know bicalutamide can do NOTHING for anyone in that year or two. I might as well be taking a sugar pill. The millions of cancer cells at work, replicating and preparing the soil for more tumors are evidenced by nearly a 90% drop in PSA in a few months.

And the fact that, in the study YOU cited, "symptomatic M1 patients [had] a statistically significant improvement in subjective response (70%) compared with castration (58%)" is probably further evidence that the cancer is running amok, with such a poor medicine.

You keep referring to STAMPEDE. Tell me where is says or implies Casodex is useless.

Better get on wikipedia and drain that page of its bad info, where we can read that bicalutamide is available for the treatment of prostate cancer in over 80 countries worldwide and is registered for use as a 150 mg/day monotherapy in at least 55 countries and "is effective for, remains approved for, and continues to be used in the treatment of LAPC and mPC" and even as of 2014 "was still the most commonly prescribed drug in the treatment of metastatic castration-resistant prostate cancer."

Oh, and has "been suggested for treating COVID-19 in men and as of May 2020 is in a phase II clinical trial for this purpose."

I'll stay on my sugar pill a little while longer, thanks.

Tall_Allen
Tall_Allen in reply to noahware

It is an outmoded therapy, no longer used as a single agent, for good reason.

gregg57
gregg57 in reply to noahware

I'm wondering if you know why doctors mainly only prescribe Bicalutamide for the T flare caused by LHRH agonists.

noahware
noahware in reply to gregg57

Yes. (And I think you mean "US docs.") There are multiple reasons. The primary one is simple: it was never FDA approved as monotherapy in the US, unlike in virtually every other advanced economy. So it is not and never has been the consensus standard of care, i.e. it is not in OUR system's past or current set-it-and-forget-it "recipe book."

The fact that bicalutamide can switch from AR antagonist to agonist makes it a potential liability for both patient and doc that requires careful attention. The easiest thing to do is leave it out, which is another main reason it is not used: easier not to. But it is still part of the protocol for docs who believe in the "Triple Androgen Blockade" of lupron, casodex and proscar used by Bob Liebowitz, Snuffy Myers and others.

ragnar2020
ragnar2020 in reply to noahware

Hi Noahware,

Thanks for this posting and your others in this string. Historical analysis helps put things in perspective. I know taking the time to read and reply on this forum and others is time consuming, but, I for one am really glad you’re doing it. Hope things are going well.

Jeff

noahware
noahware in reply to ragnar2020

Thanks, Jeff. Hope you are well, too!

It's worth not only considering historical context, but geo-political-regulatory, too. The US has a system for developing "standard-of-care" that seems as influenced by government regulation, litigation liability, mixed private-public (3rd party payer) insurance, etc as it is by actual science. Tall_Allen wants us to believe it is all about "the science" when clearly it is not!

LearnAll
LearnAll in reply to Tall_Allen

You said to me I need to get out of past. My response is that you need to get out of past as DSM IV was discontinued approx. 2 years ago. . In present, DSM 5 is being used by doctors.

LearnAll
LearnAll in reply to noahware

More and more consumers /patients are finding out about dirty game of onco-industrial complex maximizing their profits and bankrupting patients and their families. Consumer backlash has started and will grow fast as more people find out how they are being ripped off by creating excessive fear of death and then offer $3000 a month pill which is not necessarily better than older pill costing $12 a month.

Boywonder56
Boywonder56 in reply to George71

525.00 asper medicare....

I see updated SOC as taking soooo long due to the lack of trials and therefore FDA approval, what is needed is creative MO's that take each case and the data in front of them to do what is best for each patient based on each circumstance and presentation. We need both science and creativity --especially when doubling time is occurring fast and quality of life is still there. Best to all.

George71
George71 in reply to 4girls

4girls,

You are right --SOC lags 10 years behind especially in prostate cancer ... it takes 10 years to see if it really made any significance in over all survival -- many of the trials they are relying on as standard of care were started 10 years ago -they were probably designing the trial for 2 years prior to that. -- SOC is really 10 to 15 years behind doctor/clinical / patients experiences. they have new imaging capabilities that can find mets 3 or 4 years sooner and they do the same dumb thing half the time and just put people on ADT just like they have been doing 10 years ago -- some (likely many) will develop CRPC 4 years sooner.

binati
binati in reply to George71

The answer lies in the fact that SOC is dependable till a new normal is arrived at based on research and statistical significance. The time may come in the not too distant future when each of us will get individual therapies based on analysis of our body. Till then it makes sense to rely on SOC.

I value the experiences of others, but I put my faith in proven science, IE. clinical trials. One person's experience is too small of a sample to draw conclusions from. Some people here like to cherrypick the stories that support whatever point they are trying to make. For some, proving a point seems like the most important thing.

maley2711
maley2711 in reply to gregg57

It appears that way....sadly. I do believe that, in many cases, SOC might actually be standard OLD care! One simple example...continuing use of standard 12 core biopsy....obviously not the best approach, but wrongly thought to be less expensive than MRI and then biopsy. Or at least, upgrade to the use of microultrasound equipment for the initial biopsy.

gregg57 wrote >>> " ...but I put my faith in proven science, IE. clinical trials... "

Then there is myself who simply felt like NOT GOING WITH SCIENCE and instead made the possibly death hastening - illogical choice to take away with castration and replace with T injection.

Bold choice, glad it has worked out for you. I would not have known nearly enough, and still do not, about this disease to do what you did. I wish you continued success.

Only working --- *SO FAR UP TO TODAY RIGHT NOW* ;0)

Not a clue as to what later today or the tomorrows will bring other than eventual death but in the between time I want to live a life with as much QUALITY as possible and not being on ADT has helped.

Thats awesome, I haven't had a hard time on ADT so I feel for those that do. No doubt biking is good for both of us. I dodged a hawk, male pheasant and 2 Guernsey cows the other day w/o a trip to the hospital so I count myself fortunate that way as well. Watch out for those hogs :)

GREAT HANDLING on your part. On my night rides I'm actually more apt to ride onto bunny rabbits, opossum, racoon that often zig-zag right in front of me. A couple of day rides I've come upon American Bald Eagles munching on a meal. Those birds are HUGE when only a few feet from you and their talons were VERY INTIMIDATING.

We have all of those as well but the vermin are usually no longer zigging or zagging and have not seen a Bald Eagle on the road yet. Plenty in the area though. Saw quite few on road kill in Montana as well as Golden Eagles, but from a car. So I cam imagine running into one on a bike would be a shock and something to remember. My wife had one attack her ducks 10 feet away from her, she was traumatized to say the least.

Boywonder56
Boywonder56 in reply to treedown

I havent had a hard on with adt......😂🤔🙄.....beat u to it

J.o.h.n.....

Holy Sh1t guys this is like a reality soap opera show. But I am learning so much about SOC and what little choice I had with bicalutamide (a word my GP couldn't pronounce just yesterday.) to be fair she's not a specialist. So here I am being asked to start on bicalutamide for a week then Zoladex. by the SOC giver (top U in the province) who simply just said you are the driver here? Anyway I want my T and my wife would like more of it. They say well you can't have your cake and eat it to. Don't take the meds and die and by the way that's it there's nothing else. It a bit different way down under, as I have learned form all of you above the equator.

Is this tE2 expensive? and by the way I value all f your inputs here ALL., without which I will know very little indeed. Thank You All

Little Alan

Hi alangeorge,

That’s the value of these online forums. Information. Use what you learn to dig deeper, and question authority when you do not fully understand what is being presented from caregivers and if the explanation is not logical or fully explained. The PCa NCCN SOC is thé mutually arrived at road-map crated by a group of selected docs based upon the conclusions they draw from evaluating clinical trials, their personal bias, financial pressures placed upon them by their employers, their professional associations, their peers, their insurers, their malpractice attorneys,their own financial

wellbeing and the sum of what they’ve learned from their medical educations and experiences of practicing medicine on PCa patients.

Go slow, read, research, reach out to others and sort through the mystery.

Good luck,

Jeff

126 Replies?

Make that 127........

Good Luck, Good Health and Good Humor.

j-o-h-n Friday 10/02/2020 6:44 PM DST

George71
George71 in reply to j-o-h-n

128

j-o-h-n
j-o-h-n in reply to George71

CXXX (with monte)

Good Luck, Good Health and Good Humor.

j-o-h-n Friday 10/02/2020 8:31 PM DST

Great post. But all good things must come to an end. Enjoy.

Your missing the initial treatment of combo intermittent hormone therapy , taking both lupron and Bicalutamide, plus Proscar, to archive max effect.

I will do a short blurb on this shortly, as few seem to note it as the front line treatment for re-occurance pc.

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