I became hormone resistant two months ago and was perscribed enzalutamide. While it did hold my PSA down to 0.1, I found the side effects devastating. I was a 7-year veteran, having had radiation HIFU and Zoladex (quarterly), none of which prepared me for my reaction to enzalutamide. I get up in the morning, spend 1.5 hrs showering, breakfast and getting ready including travel to go to work. Do about 1.5 hrs of work and then it’s downhill all the way. It was extreme fatigue after lunch, and I just can’t even keep myself upright and have to sleep it off. Loss of appetite with a lot of stomach gas, and lose 7lbs in a matter of days. Worst is at night - insomnia and the usual get up and pee every one or two hours. Does anyone on enzalutamide have a similar experience and is there anything one can do to minimize the side effect? My oncologist just said his other patients tolerate Xtandi well. Can I expect this to slowly minimize?
Enzalutamide (Xtandi) side effect - Advanced Prostate...
Enzalutamide (Xtandi) side effect
Nal,
I have heard from one doctor that many of his patients on Enza find it tough going. Abi [Zytiga] is much easier, but the cancer can be more difficult to manage when resistance occurs.
-Patrick
The cancer can be more difficult to manage if Abi fails than if Xtandi fails? Did I understand that correctly? I haven't heard that before.
One doctor's observation. Most will not be as frank.
Here's an Australian "real-world" comparison that seems to support the claim, but the study was small, with unbalanced cohorts:
frontiersin.org/articles/10...
From a meta-analysis:
"Clinical decisions on the sequencing of therapies in CRPC remain largely consensus-based rather than evidence-based, given the lack of prospective head-to-head trials assessing efficacies of agents in relation to the sequence in which they are deployed. Here, we present a trial-level meta-analysis using data from prospective trials and retrospective studies, suggesting that enzalutamide use is associated with longer median OS and PFS compared to abiraterone in the first-line (predocetaxel) setting and that this survival improvement is further accentuated when baseline Gleason score is taken into account."
hindawi.com/journals/pc/201...
-Patrick
Thanks. I've heard conflicting things, so I'll read through that. I've never had either, just 3.5 years of Lupron.
You didn't have another hormone supresant, such as Bicalutamide in combination with Lupron injections before moving on to Enzalutamide?
I had bicalutamide for three weeks before beginning Lupron, and three weeks after. No AA or Enzalitamide.
I see. My husband was on Bicalutamide and Lupron continuously for 3 years. Before, during and after radiation. When PSA started to spike switched to Enzalutamide in 2019. Slight rise in PSA is now starting again. It's interesting to read how treatments vary, but everyone's system and cancer responds differently. Good luck.
Thank you, and same to your husband. Thus far, I've been lucky with Lupron only for 3.5+ years. Last week's PSA dropped from 0.74 in March to 0.66. My MO and I discuss adding to Lupron each visit, but the longer I've been on it, the more he's inclined against it while I'm stable. As you say, doctors are doing various regimens, and how they use bicalutamide is certainly of those elements.
I do not have the link right now, Patrick. But was there not a study that brought in second line agents after the first had failed? And it showed that abiraterone +p followed by enzalutamide at failure had better PFS than enzalutamide followed by abi +p. ?
Paul,
Spanish study from last year:
"Significant clinical efficacy of AAP administered as the first-line treatment in mCRPC patients followed by enzalutamide, delaying disease progression, compared with the ENZ → AAP sequence. However, more studies and randomized trials are needed, to validate the best treatment sequencing."
Also from 2021, an Australian paper (+Johann de Bono) [2]
"Better survival outcomes were reported in several studies where patients with advanced prostate cancer received the abiraterone to enzalutamide sequence compared with the enzalutamide to abiraterone sequence."
A 2020 meta-analysis [3]:
"ABI-to-ENZ sequential therapy in patients with CRPC was associated with better PFS, PSA-PFS, and PSA response rates. Regardless of sequencing, response to drug therapy was transient for both ABI and ENZ when either agent was used as a secondary therapy. Despite this, treatment sequencing is important to achieve the maximum possible benefit from available drugs in CRPC."
Cross-resistance, of course, is a big problem - making the use of both drugs sequentially unattractive. The word "transient" doesn't give one much hope. I wonder what the percentages are for immediate resistance to the second drug? See [5].
Better "progression-free survival (PFS)" does not necessarily mean better overall survival.
Another meta-analysis (2-19) [4]:
"The current meta-analysis revealed that ABI-ENZA had a significantly more favorable oncological outcome, but the level of evidence was low."
Canadian study(2019) [5]:
"Enzalutamide showed activity as a second-line novel androgen receptor pathway inhibitor, whereas abiraterone acetate did not, leading to a longer time to second PSA progression for the sequence of abiraterone followed by enzalutamide than with the opposite treatment sequence. Our data suggest that using a sequencing strategy of abiraterone acetate followed by enzalutamide provides the greatest clinical benefit."
So, if the plan is to use both, Abi-->Enza is best. But one should consider other options.
***
I did not look at older papers.
-Patrick
[1] pubmed.ncbi.nlm.nih.gov/334...
[2] pubmed.ncbi.nlm.nih.gov/322...
[3] pubmed.ncbi.nlm.nih.gov/321...
[4] pubmed.ncbi.nlm.nih.gov/318...
[5] pubmed.ncbi.nlm.nih.gov/317...
Thank you, Patrick
I have read that also.
Have your doc switch you to zytiga. If zytiga doesn't work for you then try casodex.
Hello, I know this sounds overly simplistic but when are you taking Xtandi? Sleeping during the day and wide awake at night makes me think you are taking it in the morning. Try taking it at night!
I take it in the late afternoon before dinner
My husband switched to taking it before bedtime, does better with handling the fatigue .good luck and hope you feel better soon
I have also wondered about the time taken. Directions say better to take in morning. (?) Anyway, my husband also has narcolepsy, so he sleeps on and off 24/7!
Hi. In England, since Covid started, they now start you on Enzalutamide along with ADT and you keep taking this until failure. However, if you have the types of side effects that you mention, they will switch you in the first 3 months to Zytiga. I've luckily been ok on Enza but it is accepted by the Oncologists (and NICE who approve the drugs here) that some patients need to switch quickly. Good luck.
Try switching to abiraterone+prednisone. The only thing I know of that fights fatigue is exercise. Some guys who can afford it, get a trainer at the gym.
My husband had similar problems with Xtandi, so you are not alone. He had to stop taking it after five weeks. In retrospect we should have stopped sooner but we just kept hoping that things would improve.
It takes much longer for the body to adjust to Xtandi. It's a strong medication.
My husband did not tolerate Xtandi. Was only able to take the drug for 2 months due to larger lesions and PSA did not go down. Fatigue is constantly a problem and has been for several years. He does try to push through the fatigue by walking as much as possible. He also reads a book before he goes to bed which helps him fall asleep faster. Getting up during the night to go to the bathroom multiple times is also a problem no matter the drug he's on.
Hi cyr7 ….
I think that only about 8-12% of Xtandi users experience the severe side effects. Lotsa guys here use it with little to no SEs to speak of. You sound like you place someplace midway in between.
Unfortunately, I’m in the severe side effects group and , in my case, the side effects “ do not “ moderate over time. I don’t have your insomnia or weight loss SEs …. I put on weight and have become an Xtandi invalid , needing a wheelchair or power chair for mobility. My SE list is extensive and trying to work at a job would be out of the question. I can easily sleep 12-14 hours every day and feel totally exhausted to the point that I get red faced and huff and puff gasping for air just getting from my kitchen out to my truck in the garage.
Having said all that, Xtandi has been a life saver for me. I tried xtandi on the Eve (/so to speak ) of entering hospice , expected to live for only a few weeks or less …. Xtandi immediately stopped my decline into death and has given me 44 months of additional life. I pull up my big boy pants and get on with my life as much as Xtandi will allow …. The thought being alive is preferable to death …. even in the face of all my debilitating SEs. I can easily understand how guys would find this life unacceptable … heck … so do I …but I want to live. “ If it’s working , don’t mess with it “ the motto yayahahahaya.
I got used to managing the side effects with work arounds … can’t walk into stores or restaurants…. carry and use a mobility electric cart … can’t get up off the couch ( too weak ) 10-15 times a day( 5-7 times at night ) to pee, keep pee bottles next to my couch … can’t easily get out of bed at night ( takes a lot off effort and my equilibrium while getting up is junk ) , pee bottles next to the bed.
This is just my antidotal experience, obviously your own experience will vary dramatically…but
I hope there is something here useful in my post that you can use. If you want to know some of my “ workarounds “ I use to improve my QOL ( if you decide to stick with it and want to get on with things while using it ) and get on with life, just pm me . I’ll be glad to share what I do. Once again , I’m not advocating enduring this kind of life style , it’s the choice I’ve made to stay alive, and Xtandi has performed amazingly … keeping my 1400-1600 psa cancer undetectable.
Love brother ❤️❤️❤️
Thanks for your advice. Nice to know one is not alone
You aren’t alone on this group brother … it’s a brotherhood of great guys and gals. Lots of first rate PCa medical knowledge and compassionate hearts. A great place to hang to be part of the family.
❤️❤️❤️
We all learn how even though it is advanced prostate cancer, treatments and how people respond to them can vary greatly! Nothing is one size fits all with cancer.
Do u take Lupron with it?
Yes …. Lupron Xtandi Zometa
Yeah , I'm 10 years out on that combo. I also take Celebrex,,,
You da man … I’m hoping for some of that for myself. Show my whole medical crew I’m not croak bait just yet yayahahahaya. Good for you.
❤️😁❤️
A complete invalid on 160 mg/ dose. 80 mg worked for 3 years holding PSA to low levels. 0.012/0.013 then undetectable. With BCA PSA climbed quickly with clear scans. Got Na-F18 scan which showed mets which were zapped. Bought be another 7 mo. before popping up again.
Will talk to my oncologist about a reduced dosage. This is my 7th week, the first 4 was ok, so will discuss with him whether to cut to 80mg or 120mg. Do you need to update your PSA test to monthly to ensure Pca doesn’t rear its ugly head?
When my PSA dropped with Xtandi and taxetere and I stayed on xtandi after chemo finished, I became and invalid. Cut Xtandi and got lots better . I resumed work and my MO told me I was in complete remission. Then went to 3 mo. PSA readings for 3 years. At that time my new MO commented I was reaching the time when xtandi usually fails and I went to 30 day tests.. Made it another 6 mo. before PSA took off and Na-F18 scan showed new mets. Stayed on xtandi and I am still taking it. Supposedly the new mutation that it doesn't control can be handled by my RO and the xtandi will keep the rest under control. It's not working really great. Two BCR in bones and after radiation treatments PSA dropped for only about 7 mo. but the pain went away for most of that time. Now after second Radiation Treatment without PSA drop I am on Xofigo and PSA is still climbing. Hoping it will kill the micromets in bones and I can carry on for a few more years. Working into my 6th year of stage 4 so I'm on the upper downward side of their Bell curve. Wishing us both good luck with our treatments and a painless future. Life Is Good, but I get pretty tired after 3-4 hrs of working tilling my garden for this yrs plantings.
Doctors sugar coat the side effects no question. If they told the truth it would be pointless because it works. Why rattle the poor patient?
For most, abiraterone is far easier to tolerate, but overall, the severity of all the sides-especially the fatigue-are more pronounced in those who are overweight, have metabolic syndrome, or other co morbidities. Any and all of them correlate strongly to inability to tolerate side effects.
Lack of exercise is usually present in the same group of men, and obviously is a synergistic culprit. How much do you exercise and what kind?
I can only do short walks - 20 min or so. What the fatigue do is befuddle my head and as a result my balance is suspect. Having drastically lose 7 lbs and my leg muscles have noticeable reduced, I’m not keen to push myself and risk a fall and break some bones. Covid has meant all the gyms closed too, so that’s no help
Stationary bike, elliptical, rowing machine are all good for cardiovascular exercise, your balance won’t factor in. If your only option is walking try using a walking stick.
For strength training you don’t need weights. Calisthenics or bands work equally well.
The Xtandi deteriorates your bones, exercise preserves them. Not doing it for fear of breaking bones is not a smart plan.
Gyms still closed from Covid? Where do you live?
Some guys do well on a lower dose which reduces side effects. I’ve been taking enzalutamide for over 7 years now and I found the side effects to be cumulative. After about 3 years I felt like a zombie on the full dose. My oncologist, Dr Sartor recommended I reduce the dose to 80 mg which is a half dose, he explained that many guys still do well at lower the dose. So I did and feel much better although side effects are still there. Some oncologist prescribe Ritalin or Adderol to compensate for the side effects. Of course check with your onco before tinkering with the dosage of any medication.
Ed
I take mine before bed. Seems to minimize my SE’s.
I would guess the side effects could increase the longer you are on the drug. Been on EZ for just over a year. Full dose. Not too bad side effects except more leg weakness and less endurance. Kept PSA at bay until 2 mos ago. About the the same time the side effects really ramped up. Afternoon brain fog turned me into a zombie. MO said to lower the dosage and see if it helped. Went from 4 to 3 pills with not much help, then to 2 pills and the side effects are much better. MO commented that she doubts the med is doing much for me anymore. Next getting new scans and expect to be moving on to next treatment before long. Hoping the Provenge completed in April helped slow down the rapid progression for awhile.
Good luck
My husband was in Xtandi for a year or more and tolerated it well until he had a TIA (mini stroke). He didn’t know who he was, what year it was, etc. Then we discovered that this IS one of the rarer side effects of Xtandi. He now takes Nubeqa and has had good PSA suppression, but I’m noticing some mental fogginess. Wondering about that. 
Just a caring opinion CYR7: the severity of side effects you describe are intolerable and warrant getting off that drug now rather than trying to work around them. It is stealing too much of your life. Switch to abiraterone now, as others have also suggested.
I’m taking 120 mg now. Seems to be slightly better. Thanks for the advice
CRY7. On 80mg xtandi now. Almost a clear head all day. Almost had forgotten how good it is to think
Zytiga
Thank you. I’ve reduced my dosage to 120 mg (3 pills) after consulting my oncologist. It’s been a few days and I’m feeling a little bit better. Lu-177 is my next step if Xtandi failed. I’ll keep you in mind. Thanks so much
Yes, the side effects can be quite extreme. My husband reacted the same to enzelutamide. His doctor also seemed surprised by how awful he felt. I thought maybe his age and other health issues played into it. Luckily we are retired so not having a job sure made it easier to rest. From all I have read many men have severe side effects from Xtandi. I was frustrated with his doctors attitude and his seeming surprise of bad side effects. Nothing worse than a doctor minimizing your concerns. Some are insensitive. Thankfully, the overwhelming sick feeling and loss of appetite did lessen. It takes time though. Muscle weakness and fatigue continue with the lack of testosterone though. All these types of drugs can be difficult but I have read the enzelutamide is supposed to be the most effective in slowing cancer cells from spreading so try to hang in there. I know it isn't easy. But like we all know, everyone is unique and what is good for one person might not be best for another. We got a second opinion and that doctor at least understood the side effects. He felt my husband was on the right track with treatment and he would recommend the same exact plan. We felt better for getting another opinion.
My experience with enzalutamide in addition to Eligard matches yours. Some nominal relief if I minimize carbs. Apparently exercise helps but I am so exhausted that I am lucky to walk for 15 minutes. But I have about 4 years success and can still have reasonable quality of life if I rest frequently.
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