Oligomicrometastatic cancer

VascodaGama

… if intelligent mice ran the lab ….

xNTP,

When you mentioned on “conveyor belt urologists” I recalled one survivor at the HealthBoards forum who compared urologists to ducks in their while gowns. His opinions fit well the subject of your conversations. We discussed openly about the add-ons he used in his intermittent ADT3 treatment that were providing him with longer period off drugs in his intermittent approach. He was/is a Gleason 7 but chose to treat using only ADT, done successfully during more than ten years. Thalidomide and Celebrex were his main add-ons. The treatment included concomitant three blockades with Lupron, Casodex and Finasteride.

I also do not like conveyor belt type urologists but it is difficult to find one that goes off label. In fact, specialists rarely discuss add-ons unless these are from multi-disciplinary clinical trials or have been recommended by their urological associations. Some of my golf buddies are doctors (different specialties) and I never saw them discussing medicine along the 5 hours of play. There is this consensus among doctors to never contest the other’s opinions. Sometimes they ask me about my discoveries on PCa affairs.

Traditional, medical oncologists are the ones that use add-ons to improve main treatments, in particular the ones using chemo drugs. Myers and other famous oncologists by experience and researches done along their careers use these sort of multimodal therapies (for instance the ADT3) adapting the add-ons (some nutraceuticals and some pharmas) according to the necessities of each individual patient. I know that at least an immunomodulator is incorporated in their cocktails. However, they know well the details on interactions so that they can monitor and regulate doses along the therapy. Urologists would never adventure such rough-waters.

I have thought before in thalidomide to add my continuing ADT. This drug avoids the formation of newer blood vessels which is required by the cancer to develop further. Celebrex is a COX2 inhibitor that works similarly to Aspirin, therefore avoid inflammation initiated in the formation of newer blood vessels. Aspirin was recommended by my oncologist at JH and I started taking it since 2001.

Going off road, I wonder if the road you have been down before involves the clinical trials on 5-fluorouracil for refractory PCa (1996-2001)? In those trials they did not find substantial evidence that it works well with PCa but the chemo was FDA approved for breast cancer (and others) which shares the same genes as prostate cancer. What is missing?

I am eager in reading your “technically based treatments” you are now working on.

Best wishes,

VGama

 

Georges Calvez

Technicians v scientists

Hi Vasco,

I think you are dealing with the great divide between medical professionals and researchers.
Most doctors and pharmacists like to stick to what they know will work, they are not that bothered about how it works, try talking to the average doctor about genes or endocrinology and the eyes quickly glaze.
Pharmacists collect vast libraries in their heads of drugs, illnesses and side effects, etc. Ibuprofen, tak; used for headaches, period pains, mild athritis, risk of intestinal bleeding, renal toxicity not more than three boxes of 20 x 200 mg at a time OTC, no under 18 sales.
At college they should learn some basic biochemistry but most do just enough to get an OK grade, why do more. All the pharmacy law is far more relevant and making a mistake in this area can result in an end of career event.
My team is quite focused on RP + radiation + ADT specifically degarelix for advanced cases because it has worked for them recently.
If a new paper in a big urology journal appeared with a Lupron, zinc, Celebrex, cocktail that had good results they might give it a whirl but they are work a day doctors trying to cure patients not researchers.
I suspect that particularly in the States, doing your own thing, trying something new is a good way to change your career from medicine to accountancy or such like for the average Dr Joe.
There are teams trying out novel combination therapies, here is one doing a small trial with advanced PCa using abiraterone-cabazitaxel with quite promising results, but they tend to be in teaching hospitals or research institutes.
https://www.icr.ac.uk/news-archive/prostate-cancer-drug-combination-shows-promise-in-early-trial
One problem with thalidomide is its bad reputation, you need a good reason to touch it as it can pull in a lot of flack for no good reason.
Stick thalidomide on a medical research application and the bar to getting it approved has just gone up, if it is to be used in women of child bearing age it has just gone up a lot.

Best wishes,

Georges

Georges Calvez

High bar

Hi there,

One of the problems with prostate cancer is that hormone therapy is so good that it is hard for other drugs to compete.
If you compare hormones with radio in prostate cancer with chemo plus radio in most other cancers the results are really good and the side effects are much less.
Also hormones can hold an advanced cancer for years, often decades.
Prostate cancer only kills 3% of the men who have it, a lot of cancers have kill rates like 30+ % or death is almost certain if you have an advanced case.
The current treatments are very successful, with more screening coverage we could catch it earlier and cut the patients having serious side effects even further and the death rate to close to zero, although there is the counter argument on un needed treatment.
Thus the bar to a new therapy getting into the arena is high.
If a general therapy that offered a real advance was developed it would be quickly adopted but it seems that at the moment no such break through is in the offing.

Best wishes,

Georges

xNTP

better read on 5FU...

 I am better read on 5FU drugs than PCa and realize that 5FU is not being well tested, personalized and timely optimized in PCa.  I've been down this road before..

No prior 5FU-PCa experience.  I have read over a thousand  papers with 5FU drugs and cancer (thousands of cancer papers, myriads of abstracts), read with a different center of cancer focus but not exclusion.  So I had read some about 5FU trials for PCa and they looked reasonably like earlier eras in other cancer - later geniunely useful but needed more work (or practical insight) with technique and other modulators. 

In our situation, stats were essentially 0% OS at 24 months with 5FU and 2-3 other chemo drugs without new genetically engineered drugs and a newer, lengthy, highly specialized surgery.  Even before this was fully communicated, we extended an obscure,  nicer 5FU drug in various ways, from binary component trials in humans, single component data, 5FU/analogs for other cancers, preclinical data, and directed, personal data generation over several years.  This effort was most intense before chemo and the first year of chemo and surgeries, then more routine in following years. "Virtual trials", at n=1, typically means phase 2 (on components) or often phase 1 for specific combinations, with only one mouse and many trials to do....  Nutraceuticals (and 1-2 mild off label drugs) allowed us to hot rod 5FU to do things, with more range beyond std of care, with side benefits instead of (nasty) side effects of the other chemo drugs. 

Deciphering my comments: 

Multimodal treatment:  immune therapies, chemotherapies, surgery, radiation, thermal, cryo, others many abalation

Multicomponent [chemistry, treatment]:  nutraceuticals +-  chemo +- HRT +- biologicals 

 In fact, specialists rarely discuss add-ons...

Yes, once they are out of options, we don't like the stats, treatments, or their answers... then we have to dig it out (y)ourselves.

 ...What is missing?

Accumulating old research, including clinical bits/experience of lower evidence quality, and a high quality data series for you and the bandit.

VascodaGama

that thing ....

George,

As of today I am not aware of a drug that guarantees cure in prostate cancer. Each type of treatment got its successes and falls and do not compete against each other in terms of cure. That much wanted Silver Bullet is yet to be found. Some guys comment knowing that the big pharmaceuticals are holding away medications that cure but such is not true. Researchers are in fact working trying to find that thing that manages to get to those malignant cells, destroying them (and only them) for good.
That is the challenge; trying to kill the cancer without killing the patient, by saving as much good flesh as possible. In such regard, it is necessary to stratify the bad flesh from the good one and then strip the infested out or attack it in place ransacking its living capabilities. I wonder if you meant to say competition among treatments.

Combination of drugs that address different paths (multimodal treatment) is leading us to a better approach but not to a dead end. Gene therapy may be the answer to treat with intent of real cure. I can see laboratories around the world competing to such discovery. Several steps have been done but still far to have it as a concrete measure. Meanwhile we must endure with what is available trying to extend our living moment to celebrate that day when the Silver bullet is announced.

Going deeper, I hypothesize that the switch to disconnect the living capability of malignant cells is there but not yet found. Researchers are close to it as they now recognize the switches that assure living to a cell when its existence is threatened (eg; by a present treatment). This starts of a series of mechanisms acting instantaneously to try repairing the defect. What are the strands regulating such instructions?

Genomics will in fact substitute all screening processes used in cancer. You got it or you don’t or you can modify it if interested.

Best,

VG

VascodaGama

Digging it out by ourselves

xNTP,

You are again stepping in with intrigues. Can’t you say what nutraceutical were used and list the off label drugs?

I do not think that someone reading your post will“go off half cocked”. This is a prostate cancer forum and your experience relates to a different cancer of different characteristics. Even if such an idiot would try to imitate what your “friend” did, the successful results in those side benefits represent a step forward in good medicine, worth checking before committing. Survivors of this forum are exactly giving opinions based on the evidences that they have experienced in the fight against the bandit.

You are right in recommending the many to dig out by yourself. We all should get educated on the problem even if that represents only a fraction of what doctors know. Knowing in advance what to expect gives us peace of mind when talking on the matter.
I have learned that doctors avoid becoming teachers of medicine when in consultation, and I do understand their reason. Nobody could explain the intrigues of cancer or why treatments mange to kill in such a detail, in just a mere 30 minutes of consultation. By motto doctors do not want to fail. They tend to deal with the conclusions, resuming the steps to take and covering the major consequences. Any comment or suggestion by the patient that would disturb their settings may be accepted or are simply grouped as “still in trials not yet confirmed”. Those more logic opinions get the “we can try it after”.
I can say today that usually I am well prepared to discuss with the doctor the matters of concern or medications during the short time of the consultation. I got my list of questions based on evidences and do not inquire on trivial things. They like educated patients as it avoids teaching.

My knowledge on PCa was driven by my urologist on that day when we meet and he asked me “have you decided?”
Decided what? I thought you decide for me. You are the doctor….! No, I just help you in what you decide. Go home and come again when you know what you want….

That happened in May 2000, and I am ever since reading and studying the intrigues of medicine. How our body reacts to an illness and the sequences that such an intervention unchains. In conducting my disease I try being the captain allowing the doctor to be the commandant.

I am a retired engineer used to deal with the stress involved in huge projects. I see you more as an individual connected to the medical world. Am I correct?

Best,

VG

 

xNTP

aiming

Can’t you say what nutraceutical were used and list the off label drugs?

I am loathe to simply list from another cancer, despite the majority overlap.  I've already eliminated one generic drug for clear cause. My starting point for considering a cancer is from several lists, like the Life Extension lists. Then build out with more heavy duty, specialized drug/nutraceutical  treatments that have a good story or papers, backed up with targeting and evaluation methods.  People don't take critical measurement and evaluation steps seriously for real time results, not even doctors.  Without it, people are just serially guessing and have little chance of substantial sustained changes in my observations elsewhere.

Life Extension: https://www.lifeextension.com/Magazine/2013/12/A-Natural-Arsenal-for-Prostate-Cancer-Prevention/Page-01

To me, a working treatment for advanced cancer might be

[a careful choice of one old PCa cancer drug] and/or [a select chemo drug] and a list of CAM formulas [off label drugs; nutraceuticals].  The starting place and a good convergent method are ciritical.  Undertreatment means a moving target.  Without extra surgery, we might have failed, I was able to stomp a nasty, exponential marker and stop metastasis to everybody surprise, but I knew that we needed surgery to remove surviving locations that still had another marker moving even if rising slower. 

 

...more as an individual connected to the medical world. Am I correct?

It is fair to say, where people see me (days, weeks, months), they often think I am a specialist in that area or group,  if there is a chemical or biological angle. In real life, I may follow industrial "expert failures" that occurred before me, where disaster, bankruptcy or prison have been real possibilities if there wasn't a huge turnaround in a system with complications. The younger me was aways disinterested in medicine, however my medical exposure is growing by the decade, this last decade responsible for several family members.  But I am just a draftee in the war on cancer.

VascodaGama

A draftee in the war on cancer

xNTP

Your last sentence impressed me. I would like very much to be enlisted in that war too.

Thanks for the list of natural compounds said to influence the behavior of prostatic cells (for the good or for the bad). We have in the past discussed about some of these compounds in this forum but apart from vitamin D, E and K, we seldom read about people taking them in pill form (supplements). There is a tendency by the many in getting the benefits of those compounds from rich diets that use those main ingredient. Kampoyaku in fact lists many of those described in the link you provided.
However, as George above comments, these supplements hardly reach to the level of control on the bandit as hormonal drugs do. In my lay opinion, they are not substitutes in such sense but can be taken as add-ons, if not just to calm down the mind of those taking the pill.

My inquire regarding our discussion on add-ons were focus on compounds like the Artemisinin (an anti-malaria plant compound) or radioligands like Lutetium (a metal chemical element) that are used in therapies of various cancers (still under investigation involving prostate cancer), which could include the one confronted by your friend. Something, that rarely is referred in PCa forums. In any case I will not request again the name of your add-ons.

Interestingly, Artemisinin has more than 2000 years in Kampoyaku as a compound to treat maladies like cancer. It was revived into the front medical world during the Vietnam War to treat soldiers affected by malaria. It was the cause for the 2015 Nobel Prize in Physiology and Medicine by Dr. Tu Youyou.
In trials they found Artemisinin blocking the CDK4 which is a switch for survival in PCa cells.

If interested you can read the benefits that the above could have as add-ons in a treatment for cancer;

https://www.youtube.com/watch?v=4Dh9lUbLTX0

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2629082/

https://www.urotoday.com/conference-highlights/asco-2018/asco-2018-prostate-cancer/104862-asco-2018-lutetium-177-psma617-theranostics-in-metastatic-castrate-resistant-prostate-cancer-interim-results-of-a-phase-ii-trial.html

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355374/

Best,

VG

hewhositsoncushions

Vasco

Vasco

 

However, androgen ablation treatment is associated with a 70–80% progression rate into androgen-independent prostate tumors within 1–3 years so despite the initial success of this therapy, in most cases, the cancer will relapse as an incurable hormone-refractory condition in which the overall survival is ∼15–16 months

 

Is it really that bad? We keep getting told "yea, HT will keep you going for years" but this makes it sound like CRMPC is pretty grim.

 

H

Georges Calvez

hewhositsoncushions said:

Vasco

Vasco

 

However, androgen ablation treatment is associated with a 70–80% progression rate into androgen-independent prostate tumors within 1–3 years so despite the initial success of this therapy, in most cases, the cancer will relapse as an incurable hormone-refractory condition in which the overall survival is ∼15–16 months

 

Is it really that bad? We keep getting told "yea, HT will keep you going for years" but this makes it sound like CRMPC is pretty grim.

 

H

Dancing with the devil

Hi Cushions,

That is not true for most.
Have a look at yananow to find a lot of men on intermittent hormone therapy that go on for years.
There are a lot of long term survivors on here too.
There are key factors like Gleason score; the cells in Gleason 7 cancers just do not seem to have the guts to make strong metastases whereas Gleason 10 cancers seem to metastase quickly.
But there are factors that no one yet understands, some people seem to have an immune system that does a far better job of chewing up outposts than others.
You are not going to go from a cancer that no one can even find to brown bread that quickly!
Keep the faith, have a beer!

À bientôt,

Georges

Georges Calvez

Friday night

Hi there,

I agree with Vasco on the idea that there is a cure but big pharma or anyone else is hiding it away. There are too many people working away in the same areas all the time for people to not repeatedly find the same thing.
It is like so many conspiracy theories, it requires a lot of people to lie, be bought off, etc for it to be credible.
And the rewards for anyone who breaks the silence are astronomical.
Time to take a pizza with loads of tomato and a glass of red with the wife.
This is a good global review of metastases and the immune system, I must read it in more depth tomorrow.
https://www.researchgate.net/publication/320453567_The_immune_system_in_cancer_metastasis_Friend_or_foe

Bon vendredi soir,

Georges*

*Happy comme d'habitude!

hewhositsoncushions

Georges Calvez said:

Dancing with the devil

Hi Cushions,

That is not true for most.
Have a look at yananow to find a lot of men on intermittent hormone therapy that go on for years.
There are a lot of long term survivors on here too.
There are key factors like Gleason score; the cells in Gleason 7 cancers just do not seem to have the guts to make strong metastases whereas Gleason 10 cancers seem to metastase quickly.
But there are factors that no one yet understands, some people seem to have an immune system that does a far better job of chewing up outposts than others.
You are not going to go from a cancer that no one can even find to brown bread that quickly!
Keep the faith, have a beer!

À bientôt,

Georges

Cheers George

Cheers George

Needed a lift - Apparantly I am suffering from the post SRT "down" and letting negative thoughts get to me.

H

Georges Calvez

hewhositsoncushions said:

Cheers George

Cheers George

Needed a lift - Apparantly I am suffering from the post SRT "down" and letting negative thoughts get to me.

H

Bad moments

Hi H,

We all have bad moments; both physical and moral.
I have had some truly awful ones, but hey ho we manage to pick ourselves up and go on.
Remember always, in the great majority of cases it takes a long time to die of this sh*t, most of us die of something else.

Chin up and carry on,

Georges

VascodaGama

Conspiracies

George

You may be right about existing conspiracies in medicine but I do not see a reason for big pharmas to conspire by keeping a secret about a drug that works. If you reread my above post to you I said that I am not aware of the existence of a drug that real cures. Laboratories are working on it and have reached to astonishing findings but have no Silver Bullet yet. The Pharmas managers are more interested in keeping their shareholders happy with volumes in earnings. They inflate the drugs costs according to demand and a Silver Bullet would fulfill such interest. It would be in their favor to announce it the soonest before another pharma steps in. Fortunately to us there are no conspirators like Marcus Allen (moon landing hoax) in medicine. Touch wood.

A note to Cushions; I wonder where from you got that refractory progression rates. Many factors are behind refractory and the causes depend much on the type, frequency and number of blockades. The worse scenario occurs when the cancer starts producing its own androgens for survival. This is when the bandit feels its living threatened (by the constant lack of androgens at disposal due to continuous ADT). At that moment it activates our bodies’ survival mechanisms unchaining a series of events to resist the anti cancer treatments. With an intermittent approach one manages to maintain the bandit indolent allowing periods off drugs, serving free testosterone cocktails to satisfy the buggers. Then, we strike again stopping the party. No more testosterone drinks available. Hopefully the on/off periods are repeated till we got the Silver Bullet or just till when we revisit the moon. 

Best to you all.

VG

lighterwood67

Touch wood

Good one.

A To touch wood or knock on wood is a superstitious action to ward off any evil consequences or bad luck, perhaps because of some recent action you've taken or untimely boasting about your good fortune (“I've never been in danger of drowning, touch wood”); it can also be a charm to bring good luck.  We need some luck around here.

Georges Calvez

Misunderstanding

Hi Vasco,

I think we have got tangled in my English.
I do not believe that Big Pharma or anyone else has found anything better than what we have now but has decided to hide it away.
As you say the rewards would be astronomical and if it worked in even one cancer the chance would be there it would work in others so getting in a global patent would potentially unlock untold future riches.
When I worked in organic synthesis we talked about blockbuster drugs, a blockbuster would make more than USD 1 billion in sales over its lifetime.
A cure for prostate cancer would be a double or triple blockbuster, if it was cheap enough doctors would give it to all the marginal cases just in case.

Best wishes,

Georges

hewhositsoncushions

@George / Vasco - you are

@George / Vasco - you are right. It is also the same logical argument that alternative medicine is either woo woo or something pharma would use. There is no way pharma would ignore some herb that some kaftan wearing hippy swears by if it really worked. There is too much medicine.

@vasco - re refractory time it was on a forum post somewhere where a PCA patient said that was what he was quoted from an onco as the average length of effective time HT works with follow on treatment adding 2-2 years on average. In the light of day, I realise in the cold light of day that the statistic is meaningless because it includes patients with all types, staging and progression of PCA so any result will be skewed. You are right baout intermittent HT but I have no idea ofthe NHS use this in anger.

 

H

Georges Calvez

Survival times
Hi Cushions,
This will will give you some idea, you are low down in the risk groups;
https://www.webmd.com/prostate-cancer/prostate-cancer-survival-rates-what-they-mean#2
https://www.cancer.org/cancer/prostate-cancer/detection-diagnosis-staging/survival-rates.htmi
https://www.cancerresearchuk.org/about-cancer/prostate-cancer/survival
https://www.cancer.net/cancer-types/prostate-cancer/stages-and-grades
So I would bet that you have a very good chance of more than 15 years so stop polishing your harp! :-)

Best wishes,

Georges

VascodaGama

where do I stand

Unfortunately the comments posted in this thread after October 26, 2018, were hijacked by the CSN IT administrators. Somehow they pulled the plug and let it drain unnoticed. The lost is big for the fantastic exchanged opinions I received from the fellas of this board. I have though in giving up with any more updates of this thread but I think it to be unfair to those that have followed my story since the beginning. I am sure that, just like me 18 years ago, many guys afflicted by the disease procure information in forums like ours and would like to know how one has faired on a treatment or activity. I recall those days in 2000 when I received so much help from the survivors at the occasion.

I cannot repeat what has been discussed or looted here but I can provide updates on my latest findings and decisions that follow the initial posts in this thread. In such regard, I want to tell that I consulted a radiotherapist (NHS) in December 2018 who requested a 68Ga-PSMA PET/CT. This exam was done on February 20 2019 under the expectancy that it would pinpoint the location(s) where the bandit hides but, for the surprise of all in the team (doctors, researchers and I), the results were negative. In other words this PSMA PET detected nothing that could be judged as metastasis of PCa. Surely this is upsetting because it leaves me out from the possibility in eradicating cancer with spot radiation. The news came from the radiotherapist that was evaluating any possibility in having rads over rads. The exam was done at the reliable research laboratory/clinic Champalimaud (one of the biggest and best in Europe in terms of facilities and staff). She commented last December that the results of the 18F-choline PET/CT done one year ago (positive findings) were not as precise as the ones done with PSMA isotope in prostate cancer cases. This time she ended the conversation by recommending me to inquire with my urologist (next meeting scheduled for end o May) about the possibility in doing a biopsy of the prostate bed to confirm the results of the 18F-CHL PET (details in above previous posts).

The false negative of the Ga68 PSMA PET surprised me very much. This is a test I believe vehemently to be the best for PCa detection but the result in my case with no gland in place and continuous increasing PSA (PSA=1.71 at the time of the exam), set me to check deeply into the PSMA world.
I read loads of papers and now I am convinced that the negative result may be due to the type of cancerous cells I have which seem to be less prone for detection via the protein/enzyme PSMA. Gleason rates of 3 and lower or benign have lesser activity in prostatic specific membrane antigens.

According to the several results from clinical trials on detection and on radionuclide treatments, lower risky cases made up of Gleason scores 6 (mine are 2+3) got the lower rates in detection and higher rates in treatment failures (LU177-PSMA therapy). On the other side of the coin, Gleason rate 4 and 5 and aggressive cases including refractory PCa got the best percentage in detection and treatment success. Another issue is that PSMA is also found in the lining of some other organs, including blood vessels, bladder cancer and colorectal cancer. Researchers at MSKCC gone further and commented that this PSMA may be the culprit causing PCa to became invasive.
I wonder if doctors in the future request a PSMA blood test before proposing any PSMA exam. This protein is found in all prostate cells, indicating higher levels when prostate cancer exists. A blood test for PSMA is highly sensitive but it does not substitute the traditional PSA in judgments.

The good of the 68Ga-PSMA PET is that its half-life is 68 minutes (long enough for a reliable exam) and the isotope can be done at any nuclear facility using a simple generator. Other isotopes require larger facilities with cyclotron capability that limits the test to a fewer number of nuclear clinics (C11 choline with just 20 minutes half-life) or to the smaller facilities that are closer enough to the cyclotron that would supply the F18 choline (half-life 110 minutes).

Here are some of the links that took me further into the papers from the studies serving in reference for the articles;

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1472940/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5886992/

https://www.mskcc.org/blog/psma-new-target-prostate-cancer-treatment

http://jnm.snmjournals.org/content/56/8/1131

https://www.sciencedirect.com/science/article/pii/S1879850017302060

 

Well, this is where I stand. Two PET exams with two different results, and a lower PSA of 1.71 (Feb 2019) down from 2.13 (Dec 2018). Adding to the mixture will be the opinion from the urologist that I doubt that will recommend a biopsy of tissues at the area affected by the radiation done in 2006. Apart from that I also doubt that any radiotherapist would want to apply more rads over rads on the fossa area (not as spots) which has received the full scope of Grays admissive (close to 42 Gy in a total of 68Gy). I may just continue with ADT till this fails.

Best wishes to my comrades.

VGama

 

hewhositsoncushions

Hey Vasco

Hey Vasco

Sorry to hear this. You seem quite frustrated at your inability to nail down the bandit. Are you still able to consider intermittent HT?

H