Zytiga and Liver Function

[Newyork6264]

was wondering if anyone else ran into this. Some back ground. Diagnosed with cancer in Nov 2019. Gleason 9, PSA 250+ with bone mets(lots of them). Started on Lupron on 12/1, Zytiga 1/1. Blood tests good until this last one (yesterday). While PSA and alk phos of gotten better. PSA from 250 to 7, Alk Phos from 900+ to 400. However on this last test my ALT (measure of liver function) has gone from 22 in last three tests to 160. Because of this my Oncologist wants me to stop Zytiga for a week, and then have a new blood test. If it’s come down will start me on Zytiga again. This has really taken the wind out of my sails. Was just climbs out of an emotional hole. Has anyone experienced this? If so how did it work out?

[Danielgreer]

Hi Newyork, I experienced the same thing. My MO put me on Abiraterone and my ALT shot up to over 300. She took me off the drug until my ALT returned to normal. I then went to half dose and within a week the same thing happened, highly ALT. I couldn’t take Abiraterone. My MO then set me up with Enzalutamide, which I wasn’t too happy about because of the cognitive SEs. I was about to start it when Darolutamide became an option. I’ve been on Darolutamide for several months and my liver enzymes have been normal. Somehow my MO got my insurance company to pay for Darolutamide. I’m hormone sensitive and my understanding is the drug is not FDA approved for that. Anyway I hope my experience can help you.

[Newyork6264 in reply to Danielgreer]

Thanks. How long were you on Abiraterobe before Alt shot up. Appreciate the input. Also good luck in your fight.

[Danielgreer in reply to Newyork6264]

I was on full dose Abiraterone for one month in the beginning. My ALT hit over 300 sometime in that time frame. I didn’t check my ALT until the end of the month on the drug. I looked at the instructions for the drug and we’re supposed to be tested every week in the beginning to check for liver impact. My understanding is that it’s relatively common to have some liver issues with Abiraterone. I think about 25% of us have a liver issue if I’m not mistaken.

[Newyork6264 in reply to Danielgreer]

Really appreciate the info. I had blood tests every two weeks and things were good for 6 weeks, then fourth test saw Alt shoot way up. Thought I was home free. Again thanks for info.

[Danielgreer in reply to Newyork6264]

My ALT was also raised by Lupron. Are you sure it’s the Abiraterone and not the Lupron? It’s way more likely that it’s the Abiraterone, but it sounds strange that you were fine for 6 weeks and then your ALT increased. Maybe that is how it happens? Anyway, did you have an ADT shot before ALT increased?

[Newyork6264 in reply to Danielgreer]

Been on Lupron for a month longer than Zytiga and those tests were all ok.

[cesces in reply to Danielgreer]

How does Darolutamide differ from Abiraterone and Enzalutamide.

Do they use different mechanisms? Side Effects? Pros & cons?

[Danielgreer in reply to cesces]

My understanding is Darolutamide for the most part doesn’t penetrate the blood brain barrier (whatever that means 😀). My MO told me that because of that, there are far less cognitive issues than Enzalutamide and Abiraterone. Also, there are a couple of mutations (T878A and F877L.34) that Daro is effective against that Enzalutamide is not. My MO tells me that Daro is a better drug than Enza and Abiraterone. I think all three drugs are androgen receptor (AR) inhibitors.

[Hirsch in reply to cesces]

Simply Daro and enzalutamide block the androgen receptor in tumor cells

Abi bocks synthesis of androgen before it gets to receptor site.

[Hidden in reply to Danielgreer]

Same cognitive issues with Zytiga. I guess it could be from lack of testosterone. No matter the brain takes a vacation on adt. Mine anyway. Short term memory and finding words was/is most notable.

[monte1111 in reply to Hidden]

I hope it's only a vacation.

[Hidden in reply to monte1111]

Intermittent plan. Doing Psa monthly. Harder for me or my dr to know how high to let it go before starting back because I had a tumor out of the prostate at less than 4. My highest psa before starting adt was 4.21. My first time off meds. I’m a clinical trial of 1.

[Hidden in reply to monte1111]

Oh you mean the memory thing. Me too.

[Hidden in reply to monte1111]

One month off the drugs and I’m really waking up. Cancer probably is also.

[tango65]

"Serum aminotransferase elevations occur in up to 13% of patients treated with abiraterone compared with 1% to 8% receiving placebo, but the abnormalities are generally mild, transient and not associated with symptoms or jaundice. ALT elevations above 5 times the upper limit of normal (ULN) occur in 6% of abiraterone treated vs <1% of placebo treated subjects. Nevertheless, clinically apparent liver injury with jaundice was not reported in the preregistration trials of abiraterone, although such cases including examples of acute liver failure have been reported to the sponsor since its licensure and more widespread use. There have been no publications or descriptions of the clinical features of hepatotoxicity with jaundice associated with abiraterone therapy. The product label recommends monitoring of liver tests during therapy with abiraterone and decreasing the dose in the event of repeat elevations above 2.5 times the ULN and stopping therapy for elevations above 5 times ULN. Therapy should be stopped in the event of ALT elevations accompanied by symptoms of liver injury or jaundice."

ncbi.nlm.nih.gov/books/NBK5...

[Newyork6264 in reply to tango65]

Thank you for info.

[tango65 in reply to Newyork6264]

Best of luck.!!

[GoBucks]

I had been on Zytiga for 8 months when my ALT (& AST) started rising. My PSA was <0.01. High point for ALT was 258. I went off Zytiga for about 7 weeks. Started again at a half dose and went up to 3/4 dose. Other than one odd jump, ALT has stayed down in normal range ever since. Now in month 27. All the time PSA <0.01. Good luck with your dosage experiments.

[Newyork6264 in reply to GoBucks]

Thanks. Go info to hear.

[tallguy2]

What dose of prednisone are you taking each day to combat the adverse effects of Zytiga to the liver? I am taking 5-mg/day, a very small dose.

[Newyork6264 in reply to tallguy2]

5 mg

[tallguy2 in reply to Newyork6264]

You might ask if increasing the dosage of prednisone is an option. Please keep us posted as I am only 4 weeks into my Zytiga/prednisone regime. Best wishes.

[Newyork6264 in reply to tallguy2]

Just sent an email to my doctor asking that

[Hirsch in reply to tallguy2]

5 mg is correct dosage for hormone sensitive state

The prednisone keeps the corticosteroids levels up to snuff.

Nothing to do with liver protection

[tallguy2 in reply to Hirsch]

I am castrate-resistant.

[Hirsch in reply to tallguy2]

10 mg then per drug insert

[tallguy2 in reply to Hirsch]

Not according my MO. As long as my bloodwork stays in the normal range we will stick with the 5- mg/ day dose.

[Hirsch in reply to tallguy2]

Sounds good. Best of luck

[Newyork6264 in reply to tallguy2]

Same what my MO says.

[Canoehead]

I had liver enzymes elevate with Zytiga. Reduced dosage to 750mg/day with no improvement. Reduced dosage again to 500 mg, and that worked. I also started taking milk thistle, and I believe that helped.

[abmicro]

Those liver numbers are a problem. When I had an issue with a similar drug, Ketoconazole in 2006, I got jaundice and had to stop. I searched and found Dr Charles E Myers (retired) and he had me stop all herbal drinks I was drinking, lowered the dose, and gave me UROSODIOL to help protect my liver. I tolerated it fine after that and eventually went back up to the full dose.

[45yrsDenmark]

I had the very same issue. Diagnosed in late november 2019 (PSA 90, all 12 biopsies 4+3 = 7), started Eligard (= lupron) dec. 1st 2019 and added Zytiga (aberitarone) 1000mg/day January 1st + 2x5mg prednisolon per day. Bilirubins was 19 23rd december and 36 January 24th (European units... acceptable limits are 5-25)... But Urologist said to contunie treatment and new blood sample from February 11th showed that bilirubins were back into 5-25 with a value of 14... I heard from others, that there could be a temporarily increase the first months, but often it will come back to normal after some time... Based on my experience, I would suggest to continue and follow the liver values for some time before quitting the very important treatment that Zytiga+ADT provides. Btw, PSA has dropped steadily from the around 90 to 3

[ctflatlander]

I'm 76 yo and started abiraterone Jan 2018 full dose. I had to stop it after 3 mos because of alt/ast above normal. Reduced it to 750 after it settled to normal and it climbed again. I had to stop and restarted at 500 mg and its been a low normal ever since.. I'm undectectable Make sure you are following instructiions. Best Bob

[wilcoxsaw]

Full dose elevated alt/art to 14x normal levels. Stopped 4 weeks levels went to normal. Then tried 500mg and liver levels again rose. Stopped abi for good before it caused permanent liver damage.

[lincolnj8]

2 years ago my alkaline phosphate number was at 3000, psa at 800. been on zytiga and Lupron and prednisone for almost 2 years. It took 1 1/2 years for the alkaline phosphate number to reach normal (100). I guess the liver and the bones work together to give the alkaline phosphate number. Ate what I wanted but no alcohol ever. Hope this info helps..

[pakb]

My husband takes European Milk Thistle daily and drinks dandelion tea occasionally to help support his liver process zytiga and did with chemo as well after his liver numbers went up.

I had read about those on this site- do a search for elevated liver numbers. Hope it helps!💙

[Newyork6264]

Thanks to everyone who has provided input. Really helped educate me and made me feel better.

[leo2634]

Hi NewYork yes I had the same thing happen to me. My Doctor cut me down to 750mg. And everything was fine. My PSA has been 0.1 since first month treatment that was two years ago. Leo

[spouse21]

Same thing with my guy. He had to go on and off Zytiga twice due to elevated liver enzymes about eight weeks in. He did the milk thistle, which didn't do anything. In any case, Zytiga didn't really work for him since he developed mets while on it. So he went off it permanently and started chemo. Hopefully, your MO can adjust the timing and/or dosage so you can keep taking it for a long time without any liver issues. Many men on this forum went forward on Zytiga after liver situation resolved with some tweaking. Good luck!

[Oct18]

Don't be discouraged. I was diagnosed October 2018, gleason 9, mets in pelvis, ribs and spine, PSA 43. I always forget the first 2 shots I got in my abdomen, but I believe it was firmagon. After that, it has been lupron every 4 months, now 6 months. I started Zytiga in November 2018. After 4 months, my liver enzymes were elevated, so over the next few months, I would take 4 weeks off, and start back on a lower dose after my liver enzymes returned to a normal range only to have my liver enzymes rise again. Finally we threw in the towel on Zytiga and switched to Xtanti. I've been on it since July and my PSA is undetectable. Side note, the PSA continued to decline through all of this. I also had radiation, 5 1/2 weeks to my prostate and spot on my pelvis, followed by a few zaps to my ribs and spine. I remember the defeated feeling as I had to stop taking the Zytiga. Don't lose hope. Exercise, eat healthy, meditate, pray if you are a believer, stay positive. I'm 48 years old, a single parent of three and dealing with an 11 year old son who is going through some serious anxiety, depression, autism etc..... and God willing, I will be here for a long time to raise my kids.

[monte1111 in reply to Oct18]

I'll think of you when I think I'm having a bad day. On xtandi for 30 months now.

[Wilbur77]

NewYork, sounds like it is too soon to get discouraged as Zytiga has been described as a wonder drug for its ability to knock down testosterone and lower PSA levels. ALT of 160 is not all that high, actually, as the packaging suggest stopping the meds only after reaching 5X the ULN (Upper Limit of Normal), which is around 40-50 depending on lab. I experienced a similar situation. My ALT and AST numbers shot up after 3 months on Zytiga with 5 mg prednisone. I thought perhaps I ate too soon or something. For reference, I was diagnosed in May 2019 and immediately started Lupron, followed by HDR Brachy and IMRT. Started Zytiga about a week prior to IMRT in August. Stopped Zytiga in Nov when AST and ALT suddenly increased to 4-5X whereas they did not change at all previously. Started weekly blood tests and numbers did go down but very slowly. In January numbers went back up which was a bit of a jolt - prompting an ultrasound of the liver. Finally enzymes returned to a safe range in early February - after 3-4 months of being very careful with other drugs, vitamins, everything. Started back on Zytiga at 500 mg, but after only 1 week numbers shot up again. So no more Zytiga for me! Still waiting to see how long numbers take to return to normal this time. Hope that you, like many others here, can continue on Zytiga at a lower dose. I was PSA 25 and Gleason 9 at diagnosis, but no Lymph or bone mets. The treatment of high risk disease with the triple use of Brachy, IMRT, and hormone therapy/Zytiga is supposed to work quite well. My PSA is currently at <.06. Hope you get back to normal readings quickly!

[Scoofer33]

Unlike so many men on this forum, my experience with Abiraterone has been highly favorable and trouble-free. I have dealt with hot flashes, night sweats, cognitive issues, especially trouble accessing the proper word choice, but these were expected SE’s. I was diagnosed with mPCa Gleason 9 (5+4) cancer in 12 of 12 random cores back in 2015. Post-RALRP my PSA was 17.9 and pathology had revealed cancer in seminal vesicles with PNI but no mets in lymphnodes. Nerves were not spared. I’ve been on a full dose of Abiraterone (4x250mg daily with 5mg Prednisone 2xdaily) since 10/18. In all that time my ALT has never elevated! It sounds like what you are experiencing falls well within the general experience many are having with this drug. If you are feeling blue about this recent development you shouldn’t discount how your recent hormone treatment has changed your normal response to a mild setback. Hormone treatment is very rough on us emotionally. The fatigue levels can be mind boggling as well! Everyone here encourages you as you bravely endure!

[Rocketboy113]

Hi, I have Gleason 8 with cancer spreading to both seminal vessels, doc at MSK took me off ZYTIGA & prednisone 3 different times due to skyrocketing liver functions and totally stopped altogether.

[j-o-h-n in reply to Rocketboy113]

I hope I'm not repeating myself. FYI I'm being treated at MSK by Doctor Michael Morris...

Good Luck, Good Health and Good Humor.

j-o-h-n Wednesday 02/26/2020 5:40 PM EST

[j-o-h-n]

Where are you being treated? and who's your doctor? All info voluntary...

Good Luck, Good Health and Good Humor.

j-o-h-n Wednesday 02/26/2020 5:39 PM EST

[Newyork6264 in reply to j-o-h-n]

Live in Western NY. Got three opinions one from Sloan, one from Roswell and from Strong. Decided on Strong. They and Sloan agreed on path forward. Will be back to Sloan to review results after new tests in April.

[j-o-h-n]

Thank you for your reply... I go to Sloan also - NYC (good choice for your review)....

Good Luck, Good Health and Good Humor.

j-o-h-n Wednesday 02/26/2020 9:00 PM EST

[Rocketboy113]

Dr. Michael Zalefsky MSK Manhattan, he is GREAT!!

[Rod98168]

Hi New York, I take zytiga but only one 250 mg tablet with a high-fat meal which will make it much less toxic to your liver. And the NIH study says that it's just as effective if not more so then taking 1,000 mg of zytiga on an empty stomach. My suggestion is do the same and see what happens to your liver function test. Sincerely, Rod

[Newyork6264 in reply to Rod98168]

Thanks. I’ll look into the study v

[Rod98168]

I also take eplerenone, 50mg instead of prednisone to reduce excessive mineral corticoids. It's a potassium sparing diuretic and it's much safer than taking prednisone which weakens your immune system and bones. The dirty little secret about taking prednisone, is that most people don't need it but it was included in the new patent for zytiga. I found that I no longer have severe leg cramps at night or swelling in my calves and ankles since I've been on eplerenone. This information is also found in an NIH study.

[Newyork6264]

Thanks. Good info.