I need to choose between zytiga and xtandi since now am castrate resistant - have some very specific questions

[diller]

Summary:

Dr. wants me to to choose zytiga/pred or xtandi since now am in castrate

resistant state (lupron only does not work anymore)

and he wants me to research both re side effects and patient experiences, etc.

*** Sorry for such a long post but in past I've been told that I did not include

enough information helpful to forum members reading it, and have tried

to give better detail. And sorry for the too big spacing here - I pasted from a regular file that had proper spacing.

==============

1. lots of forum postings as well as articles and studies on both zytiga and xtandi.

I have spent hours and hours reading about people's experiences, side effects,

how long they worked, etc.

2. However, I have some specific questions on some things I don't see as much

mentioned in the forums as to patient experiences

3. I need to chose one of them soon. - now castrate resistant to lupron

and dr says to choose zytiga or xtandi to start (he not recommend darolutamide

now); lupron will continue, bone rx will start soon.

4. background - more history is a bit below:

had radiation, no surgery, no prev zytiga or xtandi or infusion chemo

after recurrence, lupron itself worked for 1 year, then did intermittent,

then back on lupron a few months before it stopped working.

see my history in section 7 below.

==================================================

5.

*** I caregive for my wife who has advanced cancer - there are no children, friends,

etc to help us - its all me doing everything from food prep,shopping,

dr interfacing, rx ordering and monitoring, ins interfacing, etc, etc

etc - she cannot do any of these things and has s/e from the chemo she has had and

oral chemo she is taking.

thus will have to hire various professionals to do all these things for her as I start having

more side effects from rx and as pca spreads more if rx not work.

(and hopefully things in place for when am not here anymore)

only mentioning this to give perspective re my concern of how either rx

might impact my caring for her. That is my main and only concern.

=============================

6. What Dr. has shared about these medications re my choice

- he has patients on both, and is ok with me starting either

- he encouraged me to research and to ask these kind of questions to fellow

patients in the forum

-dr admits that neither might work at all for some and that the length of time

they work might be very short, and that they might need to be stopped or dose

reduced due to affect of s/e, and that after dose reduction they may or may not work.

Or that for others, they might work for a longer time.

- and that often, if one of these 2 not work, the other will not.

- and that of course each of us is different and the pca is not the same

for all and that we all respond differently to any given rx, etc, etc.

- dr feels darolutamide is too new to try at this point, so am not looking

into it now

dr. does not speak of many possible s/e of the rx, which I've seen as common,

but certainly I have learned a lot about them by reading patient reports

in forums, articles and studies.

===========================================================

7. PCA history

2010 biopsy - G7(4+3) several cores 90%, other G6 cores

2011 - lupron 6 mos before/during imrt

2011 imrt - 8 weeks

no surgery, no other chemo than lupron

2015 - psa starts rising

2107 - axumin shows extensive spread to lymph nodes

2017 lupron started - psa slowly down to .1 over one year

6/2018 - 5/2019 - intermitted adt - controversial decision i know given the spread

5/2019 - psa had risen back up to 5, time to restart adt

5/2019 - axumin showed even more spread to ln and possible to bones

5/2019 - started lupron again

10/2019 - lupron stopped working - psa rising

11/2019 - dr said to choose zytiga or xtandi and stay on lupron

have had no previous infusion chemo nor zytiga nor xtandi nor any other

medication or process, except lupron

================================================================

8. My questions:

a. which rx might have less s/e in the cognitive/memory/focus/fatigue area ?

(have read that xtandi might have more of these s/e)

BUT realize that any s/e or pca progression effects on other body

systems and bones can have as serious or worse impact on my ability to take

care of her. And these other s/e could come from either of these rx.

That is, there are s/e other than cognitive/memory/focus/fatigue that could as

big or bigger impact.

=============> Any comments on this re the decision of which rx ?

=============================================================

b. re prednisone only side effects

predsone is well known to have a large laundry list of possible side effects

such as insomnia, weakness, vision issues, lowering immune system, excitement,

restlessness, irritability, mood changes, effect on potassium, lowers

muscle mass and affects bones, leg swelling and more.

(1) realize its hard to distinguish between s/e of lupron, zytiga, pred

and spread of pca itself

(2) i asked dr that since pred is needed with zytiga to replace

what zytiga takes away re adrenals (this may not be accurate

description but ok for this topic) , that is,

- that since pred is needed, would it replacing whatever it is that needs

replacement from zytiga, would that mean that the pred s/e (which are well

known and many) - would those s/e be less ?

his answer - no, if one is going to get s/e from prednisone, they will happen

in this case as well.

(3) asked dr that since pred is "low dose" ie 5 or 10mg a day, could that

mean that chance of pred s/e would be less ?

his answer - same as above, if one might get pred s/e they could get

the s/e regardless of dose.

===> Thus I think any pred only s/e that could have impact on taking

care of her could be a factor for decision of which rx ?

(4) Especially concerned about the wild mood swings that can happen

with pred - 'roid rage' - I need to get along with all sorts

of professionals and my wife as well and scary to think of that

having impact.

========== Your thoughts on any or all of these questions about pred ?

===============================================

c. xtandi s/e - ie seizures and cognitive, fatigue and other s/e

(1) re seizures - am thinking of seeing neurologist to see if any testing can see if i might

have a tendency toward seizures, since those are a rare

but still possible s/e - i've no idea if there is any kind of labs

or testing on this. will contact neurologist but really don't have time to

wait re decision of which rx.

(2) have read in forums and some articles that xtandi results in more

cognitive, focus, memory issues and some other s/e than zytiga/pred ?

(3) also for xtandi - have read that some other possible s/e like PRES/brain

issues, more falls/fractures, fatigue,

dizziness and vertigo, hypertension/cardiological, reduces appetite

and lose weight, joint pain ..., edema, neuropathy

===> that some of these might be more than same if on zytiga/pred ?

===> Your thoughts ?

================================================

d. zytiga possible s/e

re liver, neuropathy, irritability re pred, heart/cardio issues - which have

not seen as common with xtandi

I realize that liver s/e might require dose adjustment or needing to stop it

but then needing to dose reduce or stop can happen with xtandi too

also pred can be hard/impossible to stop if one stops the zytiga - one must be

very carefull in doing that -

(he will let me have liver and other lab tests every 2 weeks to start and then

ongoing monthly)

===> Your thoughts ?

======================================

e. is it good to taper start of these rx ?

could one start with lower dose and continue

without going to full dose for a few days or weeks ?

-- might this show in that short time if there are s/e already

that might be bad re requiring need to dose reduce or stop rx ?

but realize that if ok on tapered dose, would still need to monitor once on full dose.

======================================

f. OK, to summarize, my task is to choose one of these to start first -

trying to weigh potential side effects of each that might interfere with

my caregiving

and knowing that the choice might not work at all, might need to stop or dose

reduce due to s/e.

===> please let me know your thoughts on any of above questions ?

AND

===> is there one of these 2 rx to start that might more likely ensure the 2nd one will work ?

(even if s/e of that one might be worse than the other)

======================================

On a personal note related to my questions and concerns:

I know I need to make a choice - have already waited over 8 weeks since

found out was castrate resistant. And psa will keep going up.

(part of this waiting is my dealing with stress and denial and shock re the recent CR news and its impacts

on my life (compared to before when just on lupron and was not CR)

as well as the potential impact on my ability to take care of my wife as a full

time caregiver for all aspects of her care.

I realize that if goal is to stay alive longer, then these rx are one

way to hopefully do that balancing I guess any debilitating side effects of rx as well

as the cancer spread if the rx stops working which also would have

big impact on my ability to take care of her.

and thus that my putting off the decision might already be making

things even worse, given that am in CR state.

I've been very lucky in my life re health - well except for the pca, and

so I think part of my denial of current situation might relate to not

wanting to admit that this has changed and will change even more.

I guess I have been spoiled to have had relatively good health.

========> Thanks for your patience with reading this post which I realize

got to be so long, am asking for your understanding.

========> Any comments re your or others experiences re my questions above

will be greatly appreciated.

[LearnAll]

Diller....My straight suggestion will be go for Zytiga as this is the most effective medicine.

No other medicine in the World acts on all THREE sites of testosterone production, namely testicles, Adrenal gland and cancer cells themselves

I am doing very well on Lupron and Zytiga with 5 mg prednisone a day.

Not every one has bad side effects from Predni at this low dose. All I had was to increase my Blood pressure medicine somewhat to c ontrol BP.

.I only take 250 mg of Zytiga in morning with a big cup of full fat yogurt as recent research from University of Chicago has shown that 250 mg Zytiga with fatty breakfast works as good as 1000 mg of Zytiga empty stomach.

Ultimately its your decision what you want to do...this is just my 2 cents.

[Tall_Allen]

Sorry if I didn't follow that - it was hard for me to read. But your concerns about prednisone are unfounded - it is only a replacement dose. In fact, many of the side effects listed for Zytiga occur because it was not taken with enough prednisone. I think Xtandi is harder to take than Zytiga. I don't think you can get Nubiqa because you are detectably metastatic.

[cesanon in reply to Tall_Allen]

TA, you have a real nice link on your website about treatment staging. Why don't you repost that here.

[Tall_Allen in reply to cesanon]

You mean sequencing? Because it doesn't apply here. He is just getting started. His only choices are Zytiga or Xtandi because he can't risk downtime.

[cesces in reply to Tall_Allen]

My recollection was that the data was starting to support much earlier use of doxataxel?

What would be the indications for not considering it's use even this early?

[Tall_Allen in reply to cesces]

He can't afford any possible downtime because his wife is ill.

[Magnus1964]

Why not start with casodex, it has fewer side effects than zytiga or xtandi. If and when casodex fails, then go to zytiga + prednisone, then xtandi.

[Hidden]

I agree with the others, go with Zytiga plus Prednisone. More people have problems with the fatigue from Xtandi.

Also, when Zytiga becomes ineffective, there's a slightly higher success rate switching from Zytiga to Xtandi later than going the other way.

[cesces in reply to Hidden]

"Also, when Zytiga becomes ineffective, there's a slightly higher success rate switching from Zytiga to Xtandi later than going the other way."

Interesting. How generally is that accepted.

[cesanon]

You may want to ask your insurer what the copays are for zytiga vs xtandi. I noticed that my old Medicare Part D supplemental set its copays such that for all effective purposes it was only willing to reimburse one and not the other.

[Gearhead]

Diller: God bless you with your mission of caring for your wife while attending to your own illness issues. As you've learned, our experiences with meds can be quite different. My experience may be useful as one small statistical data point: One year Zytiga+Prednisone, Lupron, and Xgeva. I have most all the typical, but not too bad, SEs associated with ADT. But I can't detect any significant issues specific to Zytiga or Prednisone. My QOL is good, and maybe that's because I'm not over-focusing on my illness.

[Patrick-Turner]

At 62, in 2009, Psa 6. I was diagnosed Gleason 9, 9/9 positive biopsy samples.

doc could not remove PG after opening me because of too much Pca clinging to outside of PG, but no spread was found.

I had 2 years ADT, with EBRT after first 6mths, and that lasted until 2016, so Cosadex was added, it lasted 6 months, then Zytiga, which lasted 8mths, and at that time nobody knew which was better of Zytiga or Xtandi.

But in early 2018, Zytiga failed, so I had 5 shots of Docetaxel which moved my Psa from 12 to 45+.

Then in Nov 2018 I had 4 x shots of Lu177, and started Xtandi after 3rd shot. Psa was 25 before Lu177, is now 0.3. Bone mets healing, no soft tissue mets found in last August PsMa Ga68 scan, and no more symptoms of Pca at all.

But I expect the Lu177+Xtandi effect may not last forever, and I may need to get

more doses of Lu177, or some other tailored drug depending on DNA analysis.

If you had only a short time of success on ADT, it means you Pca may be mutating fast, and you must act fast with what may work, and then quit what does not work, and start something else asap.

If I had not got Lu177, I'd be having palliative care now.

2 x 5Mg Prednisolone is least of your worries - it merely replaces what your adrenal glands stop making when you have Zytiga.

Here in Australia, after ADT alone fails Cosadex is used first, then Zytiga, when they have failed I was not allowed to have Xtandi, because of high chance it will not work, so its then chemo, but when that fails I could buy Lu177 from Theranostic Australia.

Ever since 2016, I had 5 x PsMa scans and watched how mets began to show up in soft tissues and bones and because I had enough PsMa avidity, docs thought I would get a benefit. Maybe they are right. The chemo was said to make Psa respond to Xtandi better, so maybe that's working well, but for how long I do not know.

I've lasted 10 years since diagnosis. My Pca probably began 4 years before diagnosis when Psa was only 3 maybe, and because I had a lot of Pca with low Psa the medical system diagnosed me too late.

There's FDG scans also available now which you ought to have with PsMa scan, because you need to know if you have different forms of Pca present.

Patrick Turner.

[Schwah]

I think it’s unanimous Diller. Zytega and prednisone. I’ve done quite well with both with minimal SEs but you need to exercise.

Schwah

[DakotaDon]

I've been taking Xtandi for nearly 4 years now and the worst side effects were hot flashes and fatigue. Unfortunately, it kept my PSA down for only about 2.5 years and my PSA has begun to slowly climb back up from 0.35 to 3.50. I'm to get a PET scan w Choline in Feb to hopefully see if/where the mets are and what the next steps are. FYI, I began this journey in 1996 with RP, Radiation, Casodex and then Xtandi.

Good luck with your decision making process,

DD

[RJ-MN]

Diller, I appreciate your detailed look at this decision from so many angles; your wife has a careful & methodical caregiver!

I was on Xtandi for 64 months. It quickly brought my PSA DOWN FROM 14 to <0.01 and held it there for more than a year before allowing a very, very slow rise. It was more than 5 years before quarterly scans showed progression. Now I’ve tried Abiraterone + prednisone for 3 months but have PSA rising 10-15/month; next week I switch from prednisone to dexamethasone to see if we can help Abiraterone a bit before giving up on it.

I do not sense significant side effects with either. The first ½ year on xtandi did cause some mental fuzziness; I did not feel I was as alert a driver, for example. But this lessened after some months. Dozens of men quit my clinical trial due to extreme fatigue. I felt some of that, but I was able to stay with 1 hour/day on my elliptical machine, and I believe that helped me work through that.

With 5 years of efficacy on xtandi and seeminly zero months on zytiga I cannot be impartial. Yet, with cross resistance results may have been equally as good the other way around; we will never know. Your insurance co-pays are also significant here.

This group can share an enormous amount of experiences, and some members have professional backgrounds that enrich all of us. They widen our horizons. But in the end it is your body with its unique systems and balances; it is your cancer with its own mutations and environments, and it is your own very specific needs including those of your wife. It isn’t avoidance when we say it has to be your decision. We all live (and die)

[JoelT]

All comments are excellent, but I would also consider Nubequa if you can appeal to your insurance carrier to cover it. Unlike the other drugs it does not cross the blood brain barrier eliminating the brain and seizure issues that accompany Xtandi. As mentioned, it would be an off table use, but an appeal to the insurance company given your other issues might go through if your doctor presents the case properly. With doing your research on it.

[GARunner1 in reply to JoelT]

Found the site below that might be of help if Nubequa is pursued. Seems to be put out by Bayer, the manufacturer of the drug and has resources for advocacy to help get the drug and help in paying for it. I know nothing more than what is on the site. I pass it on for what it is worth. Hang in there and wishing you the best.

nubeqahcp.com/?utm_source=b...

[vandy69]

Hi diller,

I can only relate what Dr. Charles “Snuffy” Myers prescribed for me. The sequence was:

1. Zytiga (full dose) with prednisone. Got about a 1 1/2 year run. Developed “moon face” from pred, but it goes away.

2. Next he tried high dose Ketoconazole every 8 hours.

Many drug interactions, so be alert. Got about 1 year.

3. Lastly used Xtandi for about 1 year first time. Have continued to use Xtandi as a rechallenge after 2 rounds of 6 cycles of chemo each. In last round of chemo of 4 cycles, took Xtandi PLUS chemo.

4. Never any bone involvement. PCa mets from DX In many lymph nodes and more recently in liver.

5. This sequence has kept me alive 7 1/2 years with a minimum of SEs.

6. Have been of continual ADT from entire 7 1/2 years—Lupron alternating with Firmagon for several cycles and now on 12 week Trelstar.

7. Everyone is different and non of these treatments was disabilitating for me. Chemo can be temporarily disabling.

Best wishes. Never Give In.

Mark, Atlanta

[j-o-h-n]

Diller you have a quite a handful to deal with. You're a great caregiver and God will honor you for it... Would you be kind enough to let us know your age? location? treatment center(s)? Doctor's name(s)? and your wife's illness? All info is voluntary, but helps us help you and helps us too. Thank you....

Good Luck, Good Health and Good Humor.

j-o-h-n Friday 12/27/2019 5:19 PM EST

[herb1]

I'll jump in. I would try casodex first at the low dose (50mg/day), but would consider increasing to 150 mg, if blood values ok. Then, as someone suggested, I'd try to low dose (250mg/day) of Zytiga. (fewer side effects, way lower cost!). There's also Erleada (sp?)--the next "wonder" drug. I don't know much about it , its side effects, or when it's best used.

Would a switch to Estrogen (patches or gel) be out of order here?

[cabin in reply to herb1]

I have had both zytiga and now on xtandi and for me zytiga has worked best with less side effects

[diller]

This is diller, the original poster.

Thank all of you so much for sharing your helpful information, experiences

as well as your compassion in understanding about my caregiving situation,

though I know we all have our own situations that are just as important.

Will keep looking further at your replies and reading more on what you

all have mentioned and repost/reclarify as needed once have had a little time to do that.

And again thank all of you for your patience in reading what I realize could have been a too long post and apologize for any confusion in what I was saying or asking because of that.

Thanks again to all.

[mwykes]

Hi diller.

We diagnosed my PC in 2000 (when I was 50). It metastasized in 2015 (bone).

Zytiga and prednisone, along with continual ATD, kept the psa down for four years.

Bone scans recently began to show some minor activity, and the psa has begun to rise slowly, so we switched to 3 a day Xtandi, keeping the ADT.

The most prevalent side effect for both has been fatigue (but not so much that I couldn't function), about the same for each. The only other side effect I experienced was from the prednisone making my skin thinner and easier to bruise (at least I believe that's what it was).

[diller]

This is the original poster.

I've read your responses and read more about things mentioned; thanks again.

I wanted to conclude the thread with summarizing my original

questions by themselves; am hoping it will be clearer this way since I realize

my original post was very, very long and in hindsight, not as clear as it

should have been and the actual questions might have been lost in it.

(in the abbreviations below - s/e means side effect; z means zytiga, p means

prednisone, x means xtandi)

Since am castrate resistant, am asking these questions in context of that

situation, which is that lupron or related are not resulting in lowering

psa anymore.

Though realize perhaps for some/all of these questions it might not matter

if its about being CR or not ?

1. Feedback in this thread seems to be that more felt it better to use or start with

zytiga/prednisone vs xtandi

---> question - are the reason(s) those who felt zytiga is better or more

effective or to be taken first is because:

a. is it that you felt or experienced less s/e than xtandi in certain areas ?

b. OR that you found various z s/e less serious than most xtandi's s/e ?

(for example, that even with potential of liver issues with z that might need dose

reduction or to stop it, that those who chose zytiga first still felt it worth

it to use anyway and that it might be better or more effective than xtandi ?

(or for example, that even with needing to take p with z, and that p itself

can have a wide range of s/e - that those who chose zytiga first felt

it could be more effective than xtandi ?

c. OR that folks view the best psa response is to start with z/p rather than xtandi,

regardless of side effect considerations ?

(I realize some folks who have taken xtandi would be choosing zytiga

cause it would be whats left in these kind of rx (ignoring darolutamide

for now for this discussion)

2. Related to pred taken with zytiga, I have read in other pca postings/articles

that some have reported extreme mood swings from pred - 'roid rage as it is called --

even with the relatively small dose of p.

(ie much more than what they experienced with lupron only)

---> Questions:

- Did any of you experience that ? And if so, what was the impact on

your getting along with family, friends and doctors ?

- Or were there other s/e you had that were clear they were from

pred itself, versus being from lupron or zytiga ?

3. I guess s/e of bone loss and muscle wasting from zytiga or pred or xtandi

would just add on to same possible such s/e from lupron and/or pca spreading

to bones, and am assuming

one would be taking xgeva, et al in any case ?

or did anyone find that the added bone loss from z/p or x was much

more than just with lupron and spread of pca

4. Did you start with an initial lower doses onto your zytiga/pred or xtandi to see if any bad initial

s/e would happen even with those lower starting doses ?

however I realize even if no s/e from partial dose, I know that is no

guarantee that full dosage would not cause s/e

5. Have any of you needed to stop z/p or dose reduce it from bad liver lab values ?

or for other z s/e ? (not talking about situation where it just

did not work to control the psa)

AND if you did a dose reduction or stopping it, and that helped lessen the s/e, was the

psa still being controlled ?

AND if so, did you go back on full dose once liver values or othere s/e got better ?

(assuming other s/e got better from dose reduction or stopping it for awhile)

6. Same question as #5 for xtandi

7. prednisone dose - were any of you allowed by dr to take just 5mg a day vs

the usual 10 mg (5mg twice a day) ?

8. Taking zytiga with food, as per some studies and protocols

---> Did you or those you know of do that and still found the psa still being controlled ?

---> If you had taken it originally without food at the usual dose,

when you lowered the dose and took it with food,

did some of the s/e become less ?

Have read the with food studies were very small and seems there

is some disagreement with its accuracy in some circles.

=== Thanks again for your responses; they are all much appreciated.