XTANDI dosage questions - do we need a different dosage to attain steady state and to maintain steady state??

[Stoneartist]

Has anyone seen – or done some calculations on Xtandi dosage? From what I can see they arrived at 160 as the standard dosage after trials showed increasing side effects at higher doses. But I cant find any reliable info on effectiveness at lower doses-

Heres my thinking:

A single dose of 160mg has a halflife of 5.8 days (actually varies from 2.8to 10.2 so every body is different). 85% is removed from the body after 77 days – which looks like some sort of exponential decay.

Taking 160mg/ day reaches a steady state after about 28 days. Is this because the body cannot absorb more – or is this steady state dose dependence??

I am thinking that if we need 160mg to ramp up to steady state – then we don’t need so much to maintain that steady state.

Before I tie my brain in knots with an excel spreadsheet – does anyone know more about this?? I feel the medical profession has too easily jumped on the blockbusting 160mg without looking at the desired concentration. When PSA is going down 160mg is great – but once the PSA in near undetectable there must be a lot fewer rogue cells and the concentration should not need to be so high.

By the way this last thought might also be relevant to ADT – how about taking a three month dose every six months.

Any ideas guys??

[marnieg46]

I don't really have any specific information on the rationale for the 160mg dose but I know when my husband raised the issue of extreme fatigue his MO said it would be fine to reduce it to 3 tables daily instead of the 4 he is presently taking. He hasn't done this as he's reluctant to reduce the effect.

I also seem to recall someone on this site saying he'd received much the same advice.

[Stoneartist in reply to marnieg46]

I agree that we should be careful with this - on the one hand there is the "hit it as hard as you can" philosophy - but on the other hand there is the "body is a delicate finely balanced machine - only do what is necessary way of thinking!!

[Magnus1964]

There are others on this forum that reduced their dosage of xtandi after being on it for a few years. They experienced the same benefit for a few more years. Be aware, everyone responds differently to medications. Ask your doctor.

[Tall_Allen]

There were Phase 1 trials to determine the best dose, balancing side effects and oncological benefit. There were also pharmacological studies. Steady-state blood concentrations rely on maintaining the prescribed input dose. It falls rapidly when input is reduced. I don't understand why anyone would try to reinvent the wheel. Perhaps the pharmacologists at Astellas and Pfizer Oncology have already studied this and can answer your questions.

[Stoneartist in reply to Tall_Allen]

Thanks TA - I will look them up!

[Shooter1 in reply to Stoneartist]

For some of us, we really had no option. I had to cut Xtandi to 80 mg daily. It had made me a complete invalid as it pushed my aPca into remission. I'm still on 80 mg 4 years after cutting back from 160 mg. Life Is Good if you are healthy enough to live it.

[Stoneartist in reply to Shooter1]

Thanks for the input Shooter. They tested and found that SEs are dose dependent and it seems - at least for some cases - the PCa stays in remission on smaller doses than 160mg. Thats what I am now trying to find more about

[larry_dammit]

Call me a coward 😢. I’ve been on the 160 now for almost 5 years and I am not about to change unless the doctor says so. 🙏🙏🙏

[EdBar]

I reduced my dosage from 160mg to 80mg per day after being on the full dose for about 4 years. The SE’s seem to be cumulative and just became too much on a full dose. The lower worked fine for about 3 years until just recently when my PSA has become detectable again although at very low levels (I use an ultra sensitive test). This likely would have occurred no matter the dose. Of course this reduction was done under the advice of my doctor, Dr. Sartor.

Ed

[Stoneartist in reply to EdBar]

Thats interesting - could it be that once the PSA has been beaten down to undetectable we need much less Xtandi to keep it down.? Thats the feeling I get - but I am not about to reduce from 160mg (just started 6 weeks ago) but I will try to find hard evidence to present to my onkologist. Many thanks for the input.

[EdBar in reply to Stoneartist]

I wouldn’t go that far, if you can tolerate the higher dose I’d stay on it, for me the SE’s became too much.

[Shooter1 in reply to EdBar]

Me too. No QoL as an invalid.... I like to be able to feed myself, get dressed, wipe my butt, etc.....

[jbskiatook]

I was on 160 for a little over a month and had Extreme constipation and sleeplessness So my doctor with without much thought said let's just go to 120 then. The way he said it, the ease that he did I think that that 120 is a sufficient amount amount anyway. At that time I did ask him about going to 80 and he definitely said No since it was so early in the treatment. I certainly will build-up a little record at 120 before asking him to take me down to 80 but but that's just my experience right now.

[tarhoosier]

I had an off period of ten months from degarelix and when psa rose from undetectable to 0.2 MO put me on 160 mg/day for six months then reduced to 40 mg/day after psa was undetectable. I stayed on that 40 mg dose for 8-10 months (4 years ago) then 80 mg when psa rose slightly then 160 again when psa rose to 0.25 and everything has been stable at those levels for 2.5 years. Side effects were not noticeably different to me between the doses.

[Stoneartist in reply to tarhoosier]

Tarhoosier - and others. Great input guys. Im getting the feeling that the medical profession has automatically prescribed max pressure on the gas without thinking. I am gonna do some calculations to see if i can show what the equivalent dose is to maintain the saturation that 160mg attains after 28 days. I know ive only been on Xtandi 6 weeks and have minimal SEs - but I would like to be ahead of the effects which have caused you to reduce - prevention is better than cure!! So thanks a lot!!!

🙏

[Zzzgott]

I(stage IV) talked with my Doctors about Xtandi SE about a year ago and they were quick to reduce the dose to 80MG Psa has stayed >.01

[NecessarilySo]

I was taking Xtandi 160 per day with Lupron injection quarterly, which brought PSA down from 30+ to <0.1, but then along came some heart abnormalities (high Q/T interval) and hypertension and MO decided to cut Xtandi off completely. That was six months ago. My PSA has levelled off at <0.1 and I am still off of the Xtandi. Hypertension remains. I guess the plan is to restart Xtandi IF the PSA rises. So I tend to think that the Xtandi is important when you are bringing the PSA down but once it has hit bottom the Xtandi is no longer needed or it may just be eating your wallet. Of course, everyone is different and the monster does whatever it feels like.😓

[33947]

I too found that the SE of the 160 dose was just more than I was willing to handle. While my PSA dropped rapidly once I started Xtandi the fatigue and mental fogginess gradually increased over the first four months the 160 regimen to the point that was continually exhausted and my mental acuity was shot. On the suggestion of my MO I lowered my dosage first to 120mg and a few months later to 80 where I am today. PSA has continued to decline (now <0.2 from the 4.44 pre Xtandi) albeit more slowly on the lower dose. I now experience considerably less fatigue and mental fogginess than I did on the higher dosages.

[Jaguarxj]

So I have been on Xtandi now about 6 months along with zolidex every 3 months. Started out with 4 daily for 2 months and then my MO decided it's going to be 3 every day. Been doing 3 for 3 months just got checked out all good PSA is at 0.02 undetectable. So 3 days ago he decided that he wants me on 2 a day and not to come back for a check up for 3 months. Only problem I'm having is a slightly elevated Creatnin just on the border line of being high. Will see what happens in the next 3 months. Another thing he was adamant about is to get my 3rd covid shot a flu shot a pneumonia shot, and a shingles shot. Think I'm going to have a sore arm next week

[Stoneartist in reply to Jaguarxj]

If it was your MO who suggested this - then there is surely some guidance within the profession to indicate this is a good idea. I think I will suggest to my MO to do the same after the next PSA reading -- mine went from 4.7 to 1.0 after 1 month of Xtandi. All those shots together - you might feel a bit groggy for a day - best of luck!