Is there any validity to this concept—reducing the pressure on Pca via drug treatment?

[podsart]

When I read this article on using evolutionary strategies, I wondered about a view my dr espoused .

wired.com/story/cancer-trea...

Dr Myers’ operating hypothesis, developed towards the end of his practice , was to find the minimal drug dosage to continue to control your Pca, after you have initially gained control— achieved undetectable. He felt that this approach would reduce the pressure on the Pca cells to the minimal for control, you would extend time to resistance. He would wait 6 months between dose reductions to see if the Pca remained stable.

This is somewhat different from the article’s specific approaches but the direction of concept seems the same.

I was wondering how you guys felt about these concepts.

[YostConner]

We can all be thankful for men and women like Gatenby.

[Tall_Allen]

It seems to be true that reducing the cancer load has a greater effect on survival than the selective pressure of the drugs used to reduce the cancer load.

[cesanon in reply to Tall_Allen]

"It seems to be true that reducing the cancer load has a greater effect on survival than the selective pressure of the drugs used to reduce the cancer load."

I think the proposed concept is that if you have a low cancer load, perhaps low dose is optimal unless and until it starts to escalate. And that is when hit it as hard as you can.

Too bad there is no economic incentive for anyone to do the clinical trials with decent size populations to really test this.

[Tall_Allen in reply to cesanon]

For men with detectable metastases, one theory is that eliminating more cells as quickly as possible (with 2nd line hormonals and chemo) improves survival - this is justified by STAMPEDE, LATITUDE, and CHAARTED. The other theory is that "ADT-lite" will keep it going longer. This has not been justified for PCa. I would note, however, that intermittent ADT has never been shown to improve survival over continuous ADT.

For recurrent men with no detectable metastases, it may be true that ADT-lite is equivalent to ADT - not enough info yet.

[cesanon in reply to Tall_Allen]

"I would note, however, that intermittent ADT has never been shown to improve survival over continuous ADT."

That is a surprise. Somehow I thought that intermittent ADT had proven superior. And that continuous ADT was an out of date approach.

I guess with respect to side effects intermittent ADT is better.

[Tall_Allen in reply to cesanon]

No, iADT has never been found to be superior to continuous in survival or quality of life (over time). In most studies, they are equal. In the Hussain study, they could not rule out that intermittent may be inferior in men with few mets.

[cesanon in reply to Tall_Allen]

Very interesting. Thanks

[Hidden in reply to Tall_Allen]

Yep. One of the basis for my trial in 2004. Only difference was to alternate Adrimyacin with Taxotere weekly sling with Erustimine with on infusion drug and Keto with the other; plus Prednisone for each.

GD

[cesanon]

Hmmm

It seems that this theory is contra to the concept of double and triple ganging up treatments to kill the cancer, as indicated by some of the Studies that Tall_Allen has pointed out.

But maybe there is a way reconcile them. If you have an aggressive cancer you hit it with everything you have (as opposed to step therapy).

If you have a stable cancer that does not appear to be growing, then maybe a low level treatment may keep it where it is without generating to many mutations?

Of course the only way to really know is to do the clinical trials.

This now makes sense to me why Dr. Myers had me on low dose Avodart.

[podsart]

Thanks all

[Hidden]

Interesting read. I put in a call to Moffett to try and find out who the doc is in Oregon that ascribes to this idea. I'm in Oregon and my MO is starting to balk at me wanting to shorten the time on ADT and a second resource would be good to have available if needed.

[curious-mind1]

I remember Dr. Myers also saying that the tumor environment is also affected by what else is going on in the body: cholesterol levels, sugar, various proportions of different hormones, internal inflammation. So, in addition to directly targeting the PCa cells, it is also important to make one's body generally hostile (or less hospitable) to PCa cells. This is where it begins to get tough on knowing what to do exactly, and there are large variations between different doctors and their approaches, as it is more art than science at this point.

[podsart]

True; how can you (and is there) a dr who replaces dr Myers total body oversight and integration plus his research and recommendations of coordinated supplements

[curious-mind1]

Well that's the challenge we're facing. My dad's current oncologist has kept Myers' supplements under the motto: if it ain't broken yet, don't touch it.

[podsart]

Mine has done the same, also with that motto

[PhilipSZacarias]

Hello Podsart, I believe you will find the following article interesting.

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

Integrating evolutionary dynamics into treatment of metastatic castrate-resistant prostate cancer.

Zhang J1, Cunningham JJ2, Brown JS2,3, Gatenby RA4,5.

Author information

Abstract

Abiraterone treats metastatic castrate-resistant prostate cancer by inhibiting CYP17A, an enzyme for testosterone auto-production. With standard dosing, evolution of resistance with treatment failure (radiographic progression) occurs at a median of ~16.5 months. We hypothesize time to progression (TTP) could be increased by integrating evolutionary dynamics into therapy. We developed an evolutionary game theory model using Lotka-Volterra equations with three competing cancer "species": androgen dependent, androgen producing, and androgen independent. Simulations with standard abiraterone dosing demonstrate strong selection for androgen-independent cells and rapid treatment failure. Adaptive therapy, using patient-specific tumor dynamics to inform on/off treatment cycles, suppresses proliferation of androgen-independent cells and lowers cumulative drug dose. In a pilot clinical trial, 10 of 11 patients maintained stable oscillations of tumor burdens; median TTP is at least 27 months with reduced cumulative drug use of 47% of standard dosing. The outcomes show significant improvement over published studies and a contemporaneous population.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT02415621.

PMID:

29180633

PMCID:

PMC5703947

DOI:

10.1038/s41467-017-01968-5

[podsart]

Great article thanks. This adaptive strategy is a bit different from dr Myers . According to this article , max dosing followed by reduced dosing could be a problem as the the max dose period might be enough to kill too many T sensitive Pca and lead to the bad results compared to the balanced adaptive strategy. You could get a low volume tumor burden but too many Pca independent of T cells remaining.