Aplautamide, enzalutamide: low dose opinions

[Rickytarr]

Hi

Officially mcrpc. Can't get darolutamide so faced with choice of zytiga, xtandi or aplautamide in the coming weeks.

Faced with the first two I would have opted for xtandi and hopefully worked towards taking two tablets.

Maybe one but have seen a few progress at one and wonder if two would be an ideal minimal effective dose.

However, I liked the look of aplautamide but its so new so who on here has experimented with reduced dose?

Opinions please on half dose etc.

Seem to have read about numerous on this drug that have suffered with a bad rash.

Doc ants me to choose abi but I want to dodge the worries on steroids etc.

Can't help feeling that the newer aplautamide is perhaos a better bet.

Any and all opinions gratefully accepted.

Good luck

[Justfor_]

User Stoneartist uses 1/2 dosage of Enzalutamide. I use 1/7 of Bicalutamide. Both have achieved PSAs at the limit of detection. Unless you try it yourself, you will not know what will be the min effective dosage for you.

[Rickytarr in reply to Justfor_]

Thanks. High praise from cujoe, who knows his stuff.

On enzalutamide or aplautamide would you begin with full dose or immediately go for say half dose?

What's the opinion (anyone's) on aplautamide perhaps being a better bet than enzo right now.

I'm guessing that half dose (if tolerable) would be safer dose???

I liked the thinking on abi trial at the Moffitt but attempting that with strict SOC in UK would be difficult.

Thanks again

[Justfor_ in reply to Rickytarr]

Depends on the half-life of the Enzalutamide that appears to be, on average, 5.8 days. Bicalutamide has approx a comparable half-life (6-7 days), so my stepped procedure can be of interest:

I take Bicalutamide for a short duration, 10 days is my get started leg and then measure post/prior PSA. Note that it takes some 45-50 days for a fixed nominal dosage (50 mg - in the UK they are absolute in another universe by prescribing 150 mg for monotherapy) to asymptotically reach max serum concentration (flat out). That is, starting from scratch the serum concentration at day 10 is equivalent to a steady dosage of ~75% that of the nominal. If there is a reasonable PSA decline, in all RTCs this is taken as a 50% PSA decline, then reducing dosage to 75% that of previous step, it is more than certain that PSA is in a one way street, that is, descending. At closer look, there is a delay between cause and effect, i.e. the build-up of the x-lutamide serum concentration and the PSA count. So, at this point there is an under-estimation of the effectiveness of the past dosage. Think of this delay as the time it takes for the daily increase in lutamide to inactivate PCa cells. So far, I have tried twice reducing more than 75%, to exploit said delay and it worked both times. First time, I took 4 days a week the nominal dose, i.e. 57%. Second time. I tried half a tablet everyday, i.e. 50%. And so on, so forth, until an increase in PSA is recorded. Than step back to the mid-point of the latest two.

[cujoe in reply to Rickytarr]

Ricky, In reading back through this thread, I see you are already familiar with Gatenby's Abi trial. Don't know if you had found the website I linked in your follow-up post, but a short review of that is in one of the links. You might want to engage the people there for some thoughts on next treatment directions. The participation by some of the more open-minded (and internationally recognized) MOs/researchers makes that resource a unique one. I can't help but see that the patient community is getting farther and farther ahead of SOC. IMO, the use of AI is just going to make that gap wider.

Find a way to keep the gremlins from getting the upper hand and we might all make it to curative/chronic status. Time is, however, as in most things in life, truly of the essence. Best of Luck getting squared for "what's next". You're obviously a thoughtful guy, so I expect you will make a good decision.

As always, Keep it S&W, Ciao - K9

[cujoe]

Ricky - Justfor_ is the master of dose reduction. I'm working towards some reduction using bicalutamide, possibly in combination with either/and/or dutasteride and/or tamoxifen. I abandoned my earlier bical reduction test due to gynecomastia and had to temporarily stop the bical until I could get a tamoxifen (10 mg daily) script to bridge me to an RT treatment. Gyne seems under control and I am back on bicalutamide 50 mg daily to get back to undetectable. I will do a LEF Male Hormone Panel next week to see if I am there yet. Since my E2 was higher than I like at the beginning of the month, I decided to do 1/2 tab of tamoxifen every other day to see if that will knock the E2 back down in the 20s. All seat of the pants at this point. My original plan was to try a bical + dutas combo with dosage reductions to achieve a stable PSA between 0.05 and 0.1. Tamoxifen has added a third possibility into the mix that can help control a rising E2. BTW, I am metastatic and still hs.

Any of the newer "lutamides" are said to be stronger agents than the "weak" bical, but I have no personal knowledge of any of them. One of the hits against bical is that it seems to cause gynecomastia in around 70% of users. Mateobeach has/is using Darolutamide, but price is prohibitive for most without some sort of deluxe insurance or very deep pockets.

Good luck with whatever drug option(s) you choose.

Stay Safe & Well, Ciao - Kaptin K9

[Justfor_ in reply to cujoe]

Hi cujoe, when you get the results next week, please post the PSA counts before and after and the days on 50mg. In my case, 10 days gave approx. 50% of decline. Best of luck.

[cujoe in reply to Justfor_]

Justfor_, Will do. My first use of bical was a 10 day test two years ago (Thanks to Nal) and I also got a halfing of PSA from 0.24 to 0.132 (note: different labs were used). Soon after I did a 30 day trial with bical + dutasteride that reduced that result to 0.039. (= 70% reduction ~ 50% every 2 weeks.)

I stopped to test for durability, but got none. That eventually led to a free-run of PSA for PSMA scan, eventually peaking while I delayed treatment decision for 2nd reading of scan @ around PSA of 2.6. Two months of 2 lupron got me back to <0.04 PSA (T=8) - also, non-durable. (1 month later T had already rebounded to 530.)

That was when I started my "experiment" with bical dosing reduction. The booby prize threw a temporary physiological monkey-wrench into that plan, so I am now just getting back to square one. My PSA was 0.5 early this month, so I expect the 30 days of bical (+ the 1/2 tab tamoxifen) daily will get me back to "undetectable" < 0.1. The PSA component of the LEF hormone panel is standard sensitivity, so I will only know if I am <0.1. I am equally interested in seeing if the E2 has come down and % free-T as I am in the PSA reduction.

I have a regularly schedule MO appt with more-sensitive PSA + T labs in mid-July, so that will give me the real benchmark for future adjustments in combos and dosages. The real curiosity over the last several years has been the consistent rising trend in T ( when taking out late day labs and the lupron cycle). It started a gradual rise after my first 3-mo lupron treatment and subsequent 4 year treatment vacation and has continued into the current upper 700s level. Some of that is doubtlessly due to the bical use, but even much of the recent rise has come when completely off bical.

I'll definitely update next week's results here, so check back towards the end of next week, as it sometimes takes 3-4 days for results to post.

I trust all is still going well with your reduced dosing and your health is otherwise fine. If so, Keep it that way. If not, get cracking, Brother! Have a nice weekend and enjoy your bical preserved QOL! Ciao - K9 terror

[Justfor_ in reply to cujoe]

Next week I will, also, have extensive lab tests. I have two PSA predictions based on two different algorithms: a) 0.023-0.025 and b) 0.027-0.029.

[cujoe in reply to Justfor_]

That's what I call very fine-tuning. I'm thinking you should be working with these people . . .

moffitt.org/research-scienc...

[Justfor_ in reply to cujoe]

Thanks for the link cujoe. It precisely expresses my beliefs and thoughts.

[cujoe in reply to Justfor_]

Dr. Robert Gatenby was the apparent Godfather of Moffitt's Evolutionary Theory Group and I think Andy Anderson is the next in line.

moffitt.org/courage/dr-gate...

moffitt.org/research-scienc...

This article from Gatenby & team speaks directly to what you are accomplishing in your n=1 testing of dosing efficacy.

cancerletter.com/trials-and...

Similar to Dr. Edward Friedman*, (The Testosterone Treatment: How You and Your Doctor Can Fight Breast Cancer, Prostate Cancer, and Alzheimer's) these are people who are trained in mathematics and, thus, looking at the driving forces for cancer development and progression using mathematical models. When looked at from an evolutionary perspective, it is closely related to game theory. All seemingly right down your alley.

If you want to dig deeper, check YouTube for videos with Gatenby, et al. Also with your extensive records from your own dosing trial, someone at Moffitt might be very interested in direct comms with you.

Keep it S&W, Ciao - K9

[Justfor_ in reply to cujoe]

Thanks for your kind words, but my records are still in a premature stage. The transfer function of any elementary control loop system comprises two parameters: Gain and phase. For the former, I have some consistent data, for the latter, aka the cause-effect delay mentioned earlier, just a very vague idea. That's the reason for I try different algorithms. By next week I may be wisemore (sophomore) or back to the drawing board. To be continued...

[Rickytarr in reply to Justfor_]

Thanks again everyone. Have open a new topic hoping to catch some more advice from those who have not read this post. Please see my other new post on range-bounded adaptive therapy with abiberaterone.

Thanks

[Magnus1964]

Remember your not trying "kill" the cancer, you trying to "live" with the cancer. At least starting with low does may be the way go.

[NPfisherman]

Ricky,

See my post on apalutamide vs abiraterone. Patrick posted a response about another study comparing apalutamide and enzalutamide showing apalutamide to be superior. Hope this helps...

Best of luck,

Fish