Zytiga and liver

[Altamonttt]

Taking zytiga 1000mg with prednisone. lft's after 6 weeks almost 10 × upper limit normal. Down now to two times uln and MO wants me to start back on 750 mg. Sound right to anyone. TIA

[Tall_Allen]

Sounds good. I hope it's more tolerable at the lower dose.

[Altamonttt in reply to Tall_Allen]

I just talk to pharmacist that works with our oncologist group. He likes the restart at 750 mg but said 250 with low fat breakfast should work as well and could maybe less toxic to my liver, given that my alt was nearly 10 times higher than unl. Do you think there's any validity to that?

Thanks

[Tall_Allen in reply to Altamonttt]

No. The pharmacist is entirely mistaken. Fat increases absorption of abiraterone - so you would get the same amount of abiraterone in your bloodstream and the same liver toxicity with the lower dose. It's a way to save money - not a way to reduce toxicity.

[Altamontt in reply to Tall_Allen]

Thank you

[MateoBeach in reply to Tall_Allen]

Wondering if aberaterone blood level testing is generally available in the community to monitor and sensibly adjust dosing?

[Tall_Allen in reply to MateoBeach]

Not generally available, but it is possible - they did it on pharmacodynamic studies.

[GoBucks]

I went from 1000 to nothing for 7 weeks due to liver numbers. I started back at 500 and when liver numbers were ok I went to 750. Been there for 2+ years. <0.01.

[dhccpa]

Have you asked about taking 25% dose once daily after a meal? Some docs are going to that based on U Chicago study.

[Altamonttt in reply to dhccpa]

We discussed that. I opted for the 750. After one week have bloodwork done. Will report that.

[Tall_Allen in reply to dhccpa]

That would be a big mistake. Should only be done if patients can't afford a full dose.

[dhccpa in reply to Tall_Allen]

I'm not on Zytiga yet but MOs seem to be moving in the direction of the lower dose but don't know what percentage. Apparently the idea is growing.

[Tall_Allen in reply to dhccpa]

I assure you that "MOs are not moving in that direction" for patients who can afford the full dose. If you can't afford a full dose on an empty stomach, it is certainly possible. The problem is that everyone will absorb it differently, so it is hard to control the amount of the dose. For someone like Altamontt who actually needs a lower dose, it would be a big mistake because he might not actually be getting a lower dose in his blood. When you start with Zytiga, start with 1000 mg/day on an empty stomach to make sure you get the full benefit.

[dhccpa in reply to Tall_Allen]

I may have stated that imprecisely. I read about the 2018 U of Chicago study a few months ago. I then begin to hear that in my area from a couple of oncologists who recommended. Time will tell how widespread the idea becomes, but I did get the impression it was catching on. I guess we'll find out in time.

[Tall_Allen in reply to dhccpa]

The data on better absorption with fat has been around for a few years (2015) and there are arguments against it (see below). NCCN allows it as an alternative. But meanwhile, cheaper generics have become available. If it would have "caught on," I think it would have happened by now. It is definitely not a way to reduce dose by those who have to reduce toxicity.

accp1.onlinelibrary.wiley.c...

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

ascopubs.org/doi/10.1200/JC...

ascopubs.org/doi/10.1200/JC...

[Hidden in reply to dhccpa]

You are correct, dhccpa. NCCN GUIDELINES® Prostate Cancer, Version 2.2019 states:

" A randomized phase 2 noninferiority study of 75

patients with M1 CRPC compared 1,000 mg/day abiraterone with prednisone after an overnight fast with 250 mg/day after a low-fat breakfast. The primary endpoint was log change in PSA, with secondary endpoints of PSA response ($ 50%) and PFS. The primary endpoint favored the low-dose arm (log change in PSA, 21.59 vs 21.19), as did the PSA response rate (58% vs 50%), with an equal PFS of 9 months in both arms.

Noninferiority of the low dose was established according

to the predefined criteria. Therefore, abiraterone with prednisone can be given at 250 mg/day administered after a low-fat breakfast, as an alternative to the dose of 1,000 mg/day after an overnight fast. The cost saving may reduce financial toxicity and improve compliance. Food impacts absorption unpredictably; side effects should be monitored and standard dosing (1,000 mg on empty stomach) used if excess toxicity is observed on modified dosing (250 mg with food). "

[Hidden in reply to Hidden]

pubmed.ncbi.nlm.nih.gov/295...

[dhccpa in reply to Hidden]

Yes, thanks for posting.

[Tennis68]

I had the same problem and went to 500 and stayed there. PSA went to <.008 and has stayed there for more than a year. Liver is fine.

[Oct18]

yes, I eventually had to be switched to Xtandi.

[Zzzgott]

Sounds exactly like me 10 times normal liver enzymes then went back on lower dose with low fat breakfast. Enzymes back up in 5 days. Now on Xtandi which is not without side effects. Do not like the fatigue, brain fog memory loss hot flashes. so reduced to 3 pills we will see next week if the psa is still down. It appears that the Lupron may be doing the majority of the work

[Altamontt in reply to Zzzgott]

I may be following the path you are on. I restart Zytiga Monday at 750 mg. After one week will have bloodwork.

I’m already used to the side effects you mentioned. But from Lupron. Been on 21 months. But I’m used to them so I’m good.

[Zzzgott]

I was trying to say that the Xtandi had higher side effects than Zytiga for me.

[Altamontt in reply to Zzzgott]

I understood. I how lower dose Zytiga works. Lowered psa to 0.04 and stopped all bane pain from uptake in hip. But I’m really not very optimistic about being able to continue it.

[Zzzgott]

I also didn't realize until recently that my hip and bone pain that I complained to doctors about for years before being diagnosed is now much better with ADT. You may be on Xtandi next but as Tall Allen says it looks like Chemo between therapies may be best.

[Altamontt in reply to Zzzgott]

Actually I had chemo and finished July 2019.

[fmenninger]

Ditto in ny case..... my ast and alt liver enzymes soared up 5x beyond normal range.. no occasional beer/alcohol for me. After doing some due diligence and talking to some researchers I know, I found out that Janssen pharm is having issues with proper dosing of zytiga of a population of men and don’t know exactly why. This is a rather small population but still does exist. More research needs to be done to figure it out. Zytiga os a phenomenal yet powerful drug for MO’s to use in fighting aPCA but can cause liver twitching!

[Altamontt]

Absolutely. Thanks