Enzalutamide (Xtandi): Start at half standard dose to extend efficacy time span?

[KGU1]

Good Morning AllI was disgnosed 6 years ago with oligometastic prostate cancer Gleeson 8, PSA 22. Since January 2018 I have been on ADT, had docetaxel chemo in April 2018, radiotherapy to the prostate, seminal vessel and pelvis in November 2018 when PSA dropped to <0.1. PSMA PET CT scan in March 2019 showed metastasis on spine and hip joint which were treated with SBRT. In 2022 PSA started rising to 3. New PSMA scan in April 2023 showed 3 new metastasis near the prostate and PSA up to 5.4. Started Xtandi 160 mg/di in April which pushed PSA back down to <0.1 but ALT liver enzyme up to 560 (ULN 59). This forced stopping Xtandi for 4 weeks until ALT was down to 69. Restarted Xtandi 4 weeks ago on 80 mg/di. Today ALT 38 and PSA still <01. My oncology team now wants to bring the dose back up to the standard of 160 mg/di.

My question: Should I stay on 80 mg/di until PSA rises again? Would this possibly extend the overall efficacy life span of enzalutamide?

I am fit, very active and pain and side effect free apart from peripheral neuropathy in my feet caused by the chemo.

I look forward to your views, experience with Xtandi and advice. Thank you.

KGU

[Justfor_]

Check how I am doing with a Bicalutamide Minimum Effective Dosage at my Bicalutamide Maneuvers thread (monthly updates):

healthunlocked.com/prostate...

If you are "brave" or "silly" enough to follow my lead, this is the cheat sheet:

a) Break all ties with Maximum Tolerated Dosage that your docs so much trust, although it is more than certain that sooner NOR later will fail.

b) Engage in monthly ultrasensitive PSA testing.

c) Choose as your target a very low PSA value, like 0.05, but definitely over and above undetectable.

d) Adjust dosage to PSA target value. It may surprise you how low it can get. On a video presentation Dr. Bob Gatenby said that they tried this feedback adjusted drug method on animals and they noticed that the effective dosage was trending downwards with time.

healthunlocked.com/fight-pr...

And since you are in the UK check this method trialed in ovarian cancer:

healthunlocked.com/fight-pr...

[Tall_Allen]

"Should I stay on 80 mg/di until PSA rises again? Would this possibly extend the overall efficacy life span of enzalutamide?"?

No. It doesn't work like that. 160 mg/day was found in clinical trials to be the best dose to delay progression. Anything less than that would be weaker and give the cancer more ability to grow and spread. Now that your liver is used to it, there is no need to take less than needed.

[Stoneartist in reply to Tall_Allen]

TA -Can you remind us which clinical trial/reference was able to come to this conclusion??

[Tall_Allen in reply to Stoneartist]

The Phase 1 trial of Xtandi established the optimal dose.

[larry_dammit]

Hard to decide how to go forward. I was diagnosed aug of 16. Did chemo 6 rounds then in Dec. I started Xtandi full dose , been on it and adt ever since , doctor and I are happy with it Psa has stayed at 0.05 all the way through. Keep up the fight warrior

[Benkaymel in reply to larry_dammit]

Do you have regular scans and if so, what trend do the show - are the tumours stable or reducing in size?

[larry_dammit in reply to Benkaymel]

Yes I have a CT and MRI every 6 months

[Benkaymel in reply to larry_dammit]

What trend have they shown regarding the tumors? Any change?

[larry_dammit in reply to Benkaymel]

No the tumors are staying the same, not shrinking but not getting any bigger either. Doctor justuses the word stable on my condition. I’ll take that, 7 years of stable is ok with me

[Benkaymel in reply to larry_dammit]

Long may it last.

[EdBar]

Xtandi can be effective at lower doses, I was on 160mg for several years until the side effects became cumulative and really affected QOL. My MO, Dr. Sartor, reduced the dosage to 80mg and it was still effective for a couple of years, my PSA remained undetectable. Almost 2 years ago my PSA became detectable again. I asked Sartor if I should go back to 160mg and he felt it wouldn’t make a difference and told me not to beat myself up with it. I’m still on 80mg and PSA remains very low but I’ve had to have a PSMA scan when it hit 0.2 which detected a spot on a rib that I had radiated and it knocked down my PSA. Now I’ve had another rise and I’m getting scanned next week, hopefully I can keep playing whack a mole for a while before moving on to other treatments.

Ed

[RCOG2000]

40 mg plus lupron has kept me below 0.01 psa for past 8 months

[Stoneartist]

I did some experiments on this using my own PSA decline curve - which was very predictable (see my previous posts). At least for my situation the PSA decline at 80mg was the same as the decline on 120mg., and I have since concluded that while we are in virtual remission the 80mg. dose is just as effective as higher doses. The phase 1 clinical trials established the maximum tolerated dose of 160mg, but also concluded that PSA decline was also evident at all doses down to 30mg. - but dose dependamt. So if you have a mass of wayward tumours I guess the max dose of 160mg is the thing, but whilst in remission - for my case, and in agreement with my oncologist, then 80mg is enough.

[TN1932]

pubmed.ncbi.nlm.nih.gov/357...

[Kanka99]

Xtandi was able to lower my PSA from 5.4 quickly to undetectable levels. After three months, my dosage was lowered to 120mg due to worrisome sides effects such as rising BP, and serious constipation. My dosage was reduced to again to 80mg because my the side effects continued. Last August, I dropped Xtandi and started taking zytiga 1000mg. So far my PSA is undetectable, and the side effects have also improved. Fight on warriors; I feel the medicines that would cure us are coming.

[j-o-h-n]

Unfortunately I don't have an answer....... but if I did, I would be driving a brand new Maserati instead of my old Yugo.........the one with the smashed "MD" license (tag)............

Good Luck, Good Health and Good Humor.

j-o-h-n Monday 09/25/2023 10:36 PM DST