Princess Alexandra Hospital – A Novel Liver Targeted Therapy for Sarcopenia in Androgen deprived men with Prostate Cancer

[Nev Black]

Professor Ho, Dr Rhee, Dr Oleinikova and Dr Navaratnam ran a Novel Liver Targeted Therapy for Sarcopenia in Androgen deprived men with Prostate Cancer commencing in the latter part of 2016.

Sarcopenia is a component of cachexia, weakness and wasting of the body due to severe chronic illness. This leads to loss of muscle strength and fatigue. The trial papers said ‘The annualised loss of lean body mass is about 10 times that occurring with ageing. Thus sarcopenia prevention during ADT remains a major treatment frontier for prostate cancer.’

David Abrahams and I elected to join the trial as we had both been on ADT for a number of years.

Personally, I have been on Eligard continually since April 2011. I have the Ozcare nurse come to our home every twenty eight days to administer the two part injection.

The Blind Trial involved taking, by mouth, a testosterone tablet or a placebo tablet for six months.

Blood test were taken at commencement of the trial, three month and at the end of the trial. These blood test were made available to us.

We also had a DEXA Scan before and after the trial. This scan is the same as the one used for measuring bone density.

Without going into a whole lot of complicated detail, a small dose of Testosterone taken by mouth is absorbed by the stomach and then the liver. An oral dose of 40 mg/day may equal as much as 250 mg by injection. As the liver is immediately breaking down the oral dose it does not increase the levels in the testosterone in the overall circulation making it safe for men on ADT.

A recent letter from the PA said the study has now been unblinded.  

David and I were in the placebo group.

Data analysis has commenced and we will be advised of the findings in due course.  

[Rich]

Hi Nev,. 

I was participated in this trial as well.  I was in the testosterone group.

Cheers,

Rich

[Patrick Turner]

Hi All,

It seems Prince  Alexandra  Hospital has yet to disclose the results, so none of us know if taking oral Testosterone avoided Sarcopenia.

I might be just beginning to get that, because weight has dropped 2Kg in 2 months since I quit eating 8 small apples a day. But I also did many more km on bike in last 2 months, and had a second Lu177 inject a week ago, and I have more bone pains and I cannot really pin down the sum total of what's happening in my body.

 

I quote,

"Without going into a whole lot of complicated detail, a small dose of Testosterone taken by mouth is absorbed by the stomach and then the liver. An oral dose of 40 mg/day may equal as much as 250 mg by injection. As the liver is immediately breaking down the oral dose it does not increase the levels in the testosterone in the overall circulation making it safe for men on ADT."

 

It is interesting that 40mg/day orally is equal to 250mg/day injected, and 250mg = 1,750mg/week injected which I think is a huge amount because even in BAT the shock dose is 1 x 400mg injection each 3 months.

From my reasoning, one might conclude 9mg per day might be nearer to the oral daily dose.

 

Unfortunately, in newspapers, radio and TV interviews et all, anyone involved in writing reports about anything at all where figures are involved often make huge mistakes because they have ZERO mathematical abilities, and they are in a rush to tell a sensational sexed up story, hence the common term "fake news", where nobody has spent time to ensure the figures are correct.

So I cannot understand the above figures at all, but then, I iz justa bloke......

 

I have had ADT with Eligard then Lucrin since April 2010, with two pauses totalling 8 months with an alarming rise in Psa each time I paused so I was forced to continue ADT.

But from 2010 up to present, my weight has remained at about average 83kg with +/- 2 kg depending on cycled km and calorie intake. I was 82kg when I raced on bicycles at 1987-1993. 

Between say 1990 and now, weight has increased 1Kg, but it is most likely I've lost 4Kg muscle and added 5Kg of fat. The same 1Kg of 71yo muscle is weaker a kg of 40yo, which is weaker than a 30yo. Strength and endurance reduction plus muscle weight loss and power loss and fat increase means I can only average 25kph at 71 where once I averaged 30kph for the same route across town at 40.

There's a normal weakening of all body functions due to aging, and many ppl have written that we all start falling apart rapidly after 50, but when I was 60 I averaged 28kph for same route as above, so most decline has been in last my last 10 years.

But last year I re-joined a cycle group I had left 5 years ago due to knee troubles and cancer treatments et all, and 4 of the guys I once rode with were still in this group and I was still just slightly faster than them all despite having the ADT etc, etc. They all had a "full bottle of Testo" and had not had ADT + EBRT etc.

So it seems to me that some men would not get sarcopenia if they did a lot of exercize, which maybe means 10 hours a week with HR elevated 50% above resting where the resting HR was 50, due the regular 10 hours a week. Sitting around in chairs all day is OK ONLY if you exercise. Astronauts who spend months at the Space Station have to be carried from the re-entry capsule and they take some time before their wasted muscles and bones regain strength.

Anyway, I might well get sarcopenia as soon as I stop exercising if I am forced to due to bone pain and other effects caused by cancer progress. I felt indestructible just 2 weeks ago, getting 25kph speeds on bike, but that could soon change dramatically, and I have seen with other ppl who suddenly are overwhelmed by effects of cancer and its treatments.

I think I might have done better to go straight away from the failure of Zytiga + ADT to Lu177, rather than dither about with Docetaxel, which allowed Psa to double, over the 16 week time between before first chemo to before first Lu177. But I cannot say what I should have done because I don't yet know if Lu177 will give me any benefit of reducing bone mets which are now starting to stop me exercising. 

 

But I would probably welcome taking oral doses of Testosterone while not raising testo in blood, and not raising Psa, if it resulted in an increase of BD and muscle strength. Maybe if I rubbed testosterone cream onto Rodger, he might become un-shrivelled up, begin to feel pleasure, and be useful if invited inside Miss Dear Pussy. 

But I just doubt anyone can have their cake and eat it, ie, avoid effects of ADT but somehow get around it with a simple cheap pill. 

I cannot help thinking that testosterone is my worst enemy. But, the cancer probably is making all its own, so I probably could have some testo intake without encouraging the Pca by feeding it with its favourite dish.

The health of any man is really a fragile thing...…

Patrick Turner.

 

 

[Kezza2]

Hi Nev,

Thanks for the info.  I have been on ADT (Lucrin) now (with a couple of breaks) since 2001but it is since I started chemo (Docetaxel) that I have really dropped lean muscle tissue, especially in the legs.  I used to be able to leg press 160kg, but now I don't think I could press 60kg.  With only two more chemo doses to go, I am looking to try to rebuild muscle after chemo is finished.  I am looking forward to any further results that come out of the trial that may give me direction.  

[Guihan]

Sarcopenia.docx

[Guihan]

I found that article most interesting, and I wondered about its possible relevance to my current situation.

Following my radical prostatectomy in December 2003, my PSA fell to 0.1 (the lowest recordable level available to me at that time). Three years later, it started climbing again, and had reached 0.8 by September 2007.

ADT (Zoladex 3-month implants) commenced in September 2007 – two tandem implants, 3 months apart). My PSA soon fell below the recordable level. The urologist’s policy was then to do nothing until the PSA again rose to a recordable level.

By the time my 4th PSA rise had been treated under that regime, I had had eight Zoladex implants. It seemed I was locked into that treatment cycle indefinitely, and I was not happy about it. I had kept accurate records of my treatment history, and I was able to calculate both the PSA doubling time for my cancer and the PSA halving time for each Zoladex implant.

My calculations indicated that, if I had just one Zoladex implant every six months, the net effect would be a gradual dropping in my PSA level. The proof of my calculations would be in the disappearance of any recordable PSA level. With the approval of an oncologist and my GP, I commenced that new treatment regime in April 2010.

I have now had 24 Zoladex implants, and my PSA has never again been recordable.

You may wonder why this guy is writing here, if he only wants to tell us his own good-news story. Well, my problem is connected to the weight-loss thing. For some time, I have been unable to maintain my weight, and I have lost 5% of my body weight in the past 12 months. MY GP seems very concerned about this, and ordered a CT scan of my torso. That came back clean, with no sign of cancer in either organs or bone. Next, I am to have endoscopic examinations from both ends. I think his hope is that I have developed a small stomach ulcer, but he is not confident about that.

Having read this article, I sure hope my GP is right about an ulcer. But if it is not an ulcer…

I don’t think my GP will be familiar with the content of Professor Ho’s study. I am therefore left worrying about whether my weight loss could be related to my ADT treatment. Even if it is related, I can’t help wondering what on earth I can do about it. Giving up the Zoladex does not have a lot of appeal!

 

[Patrick Turner]

Hi Guihan,

If your Psa is undetectable now following a rise after RP in 2003, then perhaps you are extremely lucky because I have read so many other stories where Pca suppression has been nowhere near what you have enjoyed.

I had 3 monthly injects of Eligard for first 2.5 years of ADT. The lowest Psa nadir was 0.08 before a pause in ADT after 2 years, and 18 months after 70 Grey EBRT. For a month into the pause, nothing seemed to happen which indicated the time the ADT worked for was far longer than the 3 months between injections. Tandem implants of Zoladex were never ever mentioned to me as an option and today is the first time I have read a post about it.

 

But within 6 months after the beginning of my first ADT pause, my urologist seemed lazy and indifferent to seeing such a high Psa increase after 4 Psa tests, so I handed him with a letter telling him to refer me to an oncologist to "see me out". He seemed stunned for a minute, but gave me the referral. The oncologist was at first The Most Dour man I'd met. He read the Psa reports, looked at Gleason score and said "Your Pca is incurable and you'll have to be on ADT for the rest of your life"

I'm still seeing the same doc whose hair is turning grey after 6 years, and he has become a lot more friendly, and liked me turning up to see him always dressed in lycra, and looking much younger that I was. I was trying to stay healthy, and yet the Psa went up and down twice in two ADT pauses then went up without an ADT pause, so this onco sent me to Epworth for salvation radiation to PG for patients who had EBRT for primary Pca treatment, ie, had RT to PG, not RP. I was the first in Oz to get it, most others had had an RP. 

Cosadex was added to ADT at time of salvation IMRT and I got 6 months Psa suppression. Then I had Zytiga + ADT, and that gave 8 months, average life extension, then chemo which allowed Psa to go from 12 to 45 in 12 weeks, so now I am having Lu177 and I have ZERO idea how much longer that extends my life. Psa is 20.

 

So all of us have a different type of Pca. One guy I know has lasted 26 years since diagnosis in 1993, so I would guess his Pca is a weakling, a wussy type of Pca, easily supressed for so long, or he has a good immune system, or he's stronger than the Pca. Its hard to describe Pca this way, but all Pca varies between one man and the next. 

 

Some others have got nowhere near the ADT suppression I enjoyed, then found the blocker drugs boosted Psa.

 

If you read about long term effects of ADT, you should find doctors agree that your testicles become unable to recommence testosterone production when ADT exceeds about 4 years. So the chemical castration becomes equal to having an orchiectomy, ( balls surgically removed ). This horrid operation that offends so many men is simple quick and easy but it also offends drug companies which charge so much for ADT drugs.

 

I would guess that of the 24 implants you have , maybe 1 or 2 are supplying ADT drug but it is likely that your testicles are permanently unable to ever make testosterone again, so if you stopped ADT, then monitored testosterone levels, then maybe you would find testo levels remained low, maybe 1/40 of the middle of the normal range. This small amount of testo is made by your adrenal glands. It could be enough to keep Pca cells alive

while they are in a kind of coma. So ordinary ADT cannot ever lower testo to ZERO.

 

To get testo lower, casodex, enzalutamide and abiraterone are used to shut down parts of adrenal glands.

 

You are lucky that your Pca has not mutated to allow it to grow with a low testo level. The Pca also mutates and learns to make its own form of testo. This function, with adrenal gland is interrupted by casodex, enzal and arbi but the cancer usually mutates to get around such doctor potions. So eventually, Pca is unable to be suppressed with any known form of hormone manipulation, and then options are chemo or nuclides. Pca continues after such things are applied, and then there is not much that might save you and the toxicity of more chemo or nuclides makes life so bad with side effects you cannot take any more treatment. It seems you are long way from that. 

Pca can seem to be slow growing with long doubling time then suddenly it takes off, and the speed of Psa rise cannot be fully slowed by anything. So Pca behaviour is not always predictable. 

 

Testicle removal was the older standard treatment for all older men with any kind of prostate trouble which very often was their inability to have a decent pee. In palaces of ancient empires, eunuchs had a silver catheter tube hidden in a sleeve and for use every time they felt full, for maybe 50 years. 

Doctors in 1880 noticed that eunuchs never got prostate cancer. They did not know what testosterone was, but knew that removal of balls and willy at about age 10 resulted in no male puberty and no later Pca.  

 

Eunuchs often lived much longer than the "full bottle" blokes around them who were likely to die in battles, or poisoned, get diseases, or stabbed in the back etc, etc, etc, in the wild unruly world outside the palace.

 

If we examined an old eunuch we might see a rather slim being, not able to work hard or fight battles, but able to talk his way out of trouble and the eunuchs were indeed the communicators of the empire, the diplomats and first public servants an emperor could trust, even when put in charge of a harem.

Did these eunuchs worry about premature aging like we do with ADT? Probably not, because by the time they aged, most other ppl were all younger.

 

Anyway, anything that stops low BD and muscle loss would be very welcome, providing testosterone in blood is kept low, and so Psa does not rise. I have enjoyed cycling an average of 11,000 km per year since end of 2006, and I am now 1Kg lighter, despite ADT, so for me, exercise was key to good physical and mental health for so long, but all this could collapse if Lu177 fails to hold down Pca by means of killing many Pca cells, not just suppressing the growth of Pca cells in countless mets which probably seeded to bones many years ago, maybe before ADT started in 2010.

 

My ratio of fat to muscle weight has changed so there's more fat. Weight has not changed much. I accept the weight change so far. But a 5% weight loss would be for me going from 82Kg to 77Kg, about my weight at 25, when I had a fabulous figure. If I was 77Kg now, I'd look a bit strange with nobly knees, and I'd just look older but if weight loss was more then I'd get worried and seek whatever help I could find.

 

But maybe I just die before I need to worry about it. One needs to step outside of yourself and look back at you and ask "WTF is likely to happen to me?" Nobody can have complete control over the aging process which includes necessary treatments for illness plus side effects.

 

We should seek to live long, and well, if we enjoy living, but accept that life is temporary. 

There are billions of men who are worse off than I am.

Trying to weigh less seems to be a more common concern for most ppl but when you eat a lot with no weight gain and get thinner, it may be a big worry. A dietician might help.

A stomach ulcer is cured with antibiotic, but doubt that it is an ulcer can be addressed by having a tiny sample of it examined properly by someone who examines biopsy samples. They say worry causes weight loss. Who is not worried when they age? Maybe a psychologist? Our fears can increase with age, so we naturally become less reckless. Ppl might think I am reckless by exercising, and on a bicycle but its low speed, mainly on cycle paths or in low density traffic and total so far is 240,000km and last time I looked, the brain I have was still getting me to cycle defensively. I've been tempted to buy a motor cycle but the falls of motorcycles will do far more damage,

and there's no benefit from muscle use. I'm also reducing height as my spine slowly looses thickness of cartilage between vertebra. I can't be 6'2" any more unless I wear high heels, something not acceptable lest I generate attention I would not want 🙂.  

Patrick Turner. 

 

[Kezza2]

In light of Nev's post, I decided to research Sarcopenia.  I came upon a reference to HMB, or beta-Hydroxy beta-Methylbutyrate Monohydrate.  It appears that this compound, derived from the amino-acid Leucine, may be useful in counteracting the effects of muscle wastage, in my case brought on by chemo.  Does anyone have any additional information on this Dietary supplement ??  Has anyone used it, and is it readily available ??  I am guessing it is most likely available from the body building supplement stores.

[DaveK1200]

Hi everyone,

 

Happy New Year.

 

Patrick wrote.. 

“So all of us have a different type of Pca. One guy I know has lasted 26 years since diagnosis in 1993, so I would guess his Pca is a weakling, a wussy type of Pca, easily supressed for so long, or he has a good immune system, or he's stronger than the Pca. Its hard to describe Pca this way, but all Pca varies between one man and the next.” 

 

I'm sure he's correct, but I can't help feeling that Pca researchers should be looking long and hard at this gentleman to find out why he’s done so well.

 

They could probably find other men with a “wussy type of Pca”, (as Patrick described it), to include in a study to try to find a common link.

Perhaps it’s genetic, perhaps it’s lifestyle, or perhaps it’s something they are taking?

If researchers could find out why some men have a “wussy type of Pca”, then that might lead to something that could help others.

 

Kind regards

 

Dave

 

[Guihan]

I would just like to add a couple of footnotes to my previous posting. 

When my PCa was first diagnosed, I was able to calculate its aggressiveness. Based on my PSA values, the cancer doubling time was 187 days. By the time it reappeared after my first two Zoladex implants (3 months apart), the cancer came back much more aggressive. On its final appearance, the doubling time was down to 67 days. My urologist told be that this was the usual situation: it always comes back more aggressive than before. That is what motivated me to change my treatment regime so that I would never see that PSA again. I just had to hope that the cancer did not learn to get  by in a low-T environment.

This was no pussy-cat cancer. It scared the living daylights out of me. I acted purely on instinct, and I accept that I may well have been 'just lucky' to get away with it... (or have I?).

To return to the ADT-induced sarcopaenia topic, I have now discovered that this condition is usually associated with a companion obesity caused by fat deposits.  In my weight-loss situation, my fat was the first thing to go. I am not sure if this disqualifies ADT as a culprit. Maybe my 'wussy' prostate cancer has got me after all!

[Patrick Turner]

4 hours ago, DaveK1200 said:

If researchers could find out why some men have a “wussy type of Pca”, then that might lead to something that could help others.

Hi DaveK1200,

Happy new year, may 2019 be a year of goodness for you.

Unfortunately, nobody seems to be willing and able to afford complete analysis of all Pca patients over what might be 30 years survival after Pca diagnosis. One might think it a good idea to examine what's going on in men as their Pca grows, and also examine why most men are never going to have any problem with their PG.

For every man, 1,001 questions could be asked, and there just are not a sufficiently large army of young bright eyed and intelligent ppl who would volunteer to open the doors to the labyrinth of complexity that is every mammal. Even trying to understand a single cell is extremely difficult, let alone define how trillions of them are all  all interacting. 

I recall there was not much treatment for many cancers before 1970. It was a President Nixon who declared war on cancer and devoted huge Govt funds to cancer research which was previously funded by philanthropy, ie rich folks leaving lots of $$$ to a hospital after their beloved father died of Pca, or mother died of Bca, Oa et all. Nobody knew what would be found to cure cancer, but the question was asked, the public money flowed, and many thousands of substances derived from nature were tested, and there were so few were  successes. Finding cures for uncontrolled growth of cells ahs proved to be extremely difficult, and while a few natural chemicals did kill cancer cells, they could not be used because they killed or maimed the patient.

 

Professor Paul Davies said that the mammal DNA structure is a pyramid with primitive DNA on the base, similar to early life DNA of early life cells from many millions of years ago, and these grew with the only control being available nutrients. The succeeding upper layers of DNA are those exerting control, and cancer is a mistake in growth control so crazy lumps of uncontrolled cells develop. Early life cells were tough, able to grow in the most hostile  environment and if some doctor tips a bucket of chemo over such cells they defy the doctor by partially dying, and mutating to something worse.

So to understand enough to cure Pca might mean the amount of knowledge is huge, and the bigger the amount of knowledge the higher the $$$$$ cost of defining it. Infinite funding and a large chunk of eternity may be needed to find a sure cure for any cancer a Mr X might happen to develop.

Its is possible AI and quantum computing might make the process of understanding biology 1 million times better, faster, cheaper, and doable at home with a mobile phone app. 

I will not be here to see that happen. Meanwhile, researchers do find more things are developed to give men more lifetime, at the latter stage of their life, for example, bicalutamide, enzalutamide, abiraterone, taxanes, Lu177, Ac225, Ra223, etc.

If anyone thinks there can't be any betterment to progress, they'd be wrong, may get depressed, but life extension is welcome, and there seems to be some hope with immune therapy and despite mean life extension being only a few months. There are some who get many years, as has been the case with Provenge.

You may be sure some researchers are asking why this is so. The world cannot afford a Manhattan Project style campaign to cure cancer in old men. Not when younger ppl deserve research benefits more than old men, and it can be said the world has far larger problems to be solved before being able to get all ppl to live to an older age. 

 

Anyway, I am on Lu177, and I cannot know if it is working until scans and tests are done in 3 weeks.

 

Peter Mac is to start trial of Lu177 with added Keytruda soon. Other trials of LU177 are underway around Oz as the interest in Lu177 grows. So researchers want to hot up the action of Lu177 with added other chemicals and be guided by cancer cell DNA analysis to choose the best combination treatments give higher amount of cancer cell death for any man, to extend the benefit to more men, and to extend the mean life extension of Lu177 to more than 14 months or whatever it actually is for anyone so far. The more complex and more chemicals used may cause more and difficult side effects. Up goes the costs of treatments. 

 

We have come some way since about 1880 when doctors knew that cutting a man's balls out gave men with urination problems some relief. Chloroform allowed such serious surgery. Many of these men succumbed to Pca later, and nothing could be done, and demand for morphine increased. Now there are fentanyl implants, no need to die screaming, and so what if you die addicted to something.

 

If something simple is ever found to defeat most Pca of all men then there should be benefits found with other cancers.

But there may be limits to life extension. We might ask why not life forever? OK, how do we determine the retirement age? What effect is there on young ppl with no wealth because 80% of ppl live to 500 and have time to have enormous wealth? 

Methinks ppl would become great procrastinators if their life was eternal. Maybe infinite amounts of research is needed to cure all the other illnesses apart from Pca. 

So we all must deal with our ends, and from what I read here, most must be quietly getting on with that, not much discussion needed.

 

It is day 10 after my 2nd Lu177 shot and the slight pain in 3 of 4 bone areas has gone down but a hip is slightly tender so I am giving it time to calm down as the Lu177 radioactivity and inflammation reduces. But the after effects in hip could mean pain every time I try to cycle anywhere, and so no more cycling a merry 85km across town and back. I might expect hips to fail because my two knees needed new joints in early 2017. My sister needed both hips done before 60, and I have had EBRT to PG which meant horizontal X-ray beams went through both hips in late 2010. So hip failure might add to my bothers, with docs reluctant to operate.

There are other things I can do to be busy, and stay calm with a fast reducing future life.

Patrick Turner. 

 

[Patrick Turner]

1 hour ago, Guihan said:

n my weight-loss situation, my fat was the first thing to go. I am not sure if this disqualifies ADT as a culprit. Maybe my 'wussy' prostate cancer has got me after all!

Well, nobody can know enough about their cancer to set a date for our expiry. The uncertainty certainly remains. My Psa went up and down like a yo-yo below 8 with ADT until the added casodex, abiraterone failed, then chemo failed. It is typical Pca, with Psa up-down until nothing makes it go down and stay down.

I am at the Lu177 stage where mini Atomic Bombs have been dropped by Aunty Lutetia after she gate crashed the Pca parties in my bones. Aunty feels wounded, Pca feels bitter, and the bones are getting like Berlin in 1945, and I don't yet know who the winner is.

Patrick Turner.