Dose titration for CRPC

[Rickytarr]

Hi

For those of us who question why we should recieve the Maximum Tolerated Dose as opposed to a Minimum Effective Dose, the work of the Moffitt among others is of great interest.

In the following paper upward dose titration is of particular interest to me as I try to workout how to navigate my CRPC journey.

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

A survey of open questions in adaptive therapy: Bridging mathematics and clinical translation

Under the question: What is the optimal adaptive dose administration protocol?

I quote as follows: "In theoretical models, a tumor may be temporarily stabilized by a constant dose treatment during a short time interval. A practical question is to determine the appropriate stabilization dose. The authors found that an upward dose-titration protocol, gradually increasing the dose until the tumor is stabilized, works better than a dose reduction protocol "

Where to start with upward dose titration?

What might be the starting dose for aptalutamide or enzalutamid.

Optimal control to develop therapeutic strategies for metastatic castrate resistant prostate cancer. Journal of Theoretical Biology. 2018;459:67–78. doi: 10.1016/j.jtbi.2018.09.022. [PubMed] [CrossRef] [Google Scholar]

Optimal control to reach eco-evolutionary stability in metastatic castrate-resistant prostate cancer. PLOS ONE. 2020;15:e0243386. doi: 10.1371/journal.pone.0243386. [PMC free article] [PubMed] [CrossRef] [Google Scholar)

For me right now with a PSA of 10 and starting on 20% abiraterone, how far should I push my PSA level down?

Any and all opinions welcome.

Thanks and best wishes to all.

[Magnus1964]

Great research, thanks for sharing.

[Rickytarr in reply to Magnus1964]

Thanks magnus and especially for all yourvhard work on here for us.

[Justfor_]

Aft wind, smoother sailing. What do I mean? Dosage modulating effects, is just a very naive simplification only good for people that can't understand dynamics. It is the build up of the serum concentration of the drug that does it. With drugs having a half life of 6-7 days it will take more than a month to establish a steady state concentration. Starting from a higher dosage and reducing it, the serum concentration builds up faster. Starting from a lower one and increasing, takes much more time. But, some prefer windward sailing, it can really be fun.

[ritchiek]

Hi Rickytarr, I started taking Enzalutamide 3 years ago at a dose of 160mg daily ( 4 tablets of 40 mg , taken together once a day ). It was prescribed by Guy’s Hospital in London during the Covid-19 pandemic as it was considered that Docetaxol induced neutropenia would place men at increased risk of developing severe clinical Covid illness.

The dose remains the same , and thankfully my PSA remains ‘’ undetectable’’.

[Cooolone]

MTD vs MED is a great avenue to explore. But aside from measuring the reactive response on PCa, are we also measuring what the blood levels of the drug are? Each and every one of us are individual, as is our metabolism, which is another avenue our oncologist rarely venture into... Metabolic disease and how it all interrelates. So the MTD vs MED is very interesting indeed! Thank you for posting!

[PCaWarrior]

My MO uses MED. Adaptive therapy is attractive, and trials are underway for Zytiga and Xtandi. A study that you have likely seen is the Moffit/Gatenby Zytiga study. Small but hinted at superiority.

Modified BAT programs are another avenue. An avenue that generates libido, muscle mass, strength, energy, and bone growth among other positive effects. We have some positive data for this approach on a half dozen or so men.

An adaptive therapy that incorporates intermittent testosterone pulses might blend the best of 3 worlds. However, it has never been tried.

[Justfor_ in reply to PCaWarrior]

I may have passed, by accident, such a micro-BAT cycle and will be willing to investigate again, intensionally this time, if the opportunity arises. I call it micro-BAT because my burden is low and have plenty of endogenous Testosterone for the high T period of it (min T > 1700). The low T period is just the Bicalutamide MED to bring PSA down to less than 0.01. High T period last time was terminated at PSA 0.073 but next time will not allow it to go above 0.05. Winter is coming and there is PSA seasonality that can muddle things up.

[PCaWarrior in reply to Justfor_]

I'm doing short BAT today. 3 days of propionate, Androgel, and then oral testosterone undecanoate. 8 days later, repeat.