Resitance to Abiraterone - forever resistant?

[mypk]

Does once resistant to Abiraterone mean resistant forever, or can it work again for a while after a few months off? Any experiences?

[Tall_Allen]

The cancer has mutated to be resistant to it. There is more hope in reversing resistance to enzalutamide with chemo or BAT.

[mypk in reply to Tall_Allen]

I'm currently wondering if Abiraterone could work again after my current Cabazitaxel therapy. Abi was much more pleasant than the chemo. However, I'm pleased that I'm still alive after a PSA value of 1260 and Gleason score 9 three years ago.

I remember a small phase II study in Spain named SWITCH, which had found that 46% of patients who had become resistant to Abiraterone Acetate + Prednison responded again to AA after they were switched to Dexamethason instead of Prednison.

🌞

[StePeteMN in reply to mypk]

Congrats on finishing the Cabazitaxel; Godspeed and viel Gluck on your courageous journey. The Abiraterone will work against the cancer that is not resistant to it, and hopefully the chemo destroys much of the cancer that was resistant to the Zytiga. You don' t have one "cancer", rather many different mutations that respond to variable treatments. I finished Cabazitaxel six months ago and Pluvicto is next for me.

[mypk in reply to StePeteMN]

My Cabazitaxel infusions are not finished yet - will get my 8th 💉 on Monday. 🙂

[EdBacon in reply to mypk]

I'd try Xtandi next, I think your chances would be better than going back to Zytiga. I did Xtandi while doing my Cabazitaxel chemotherapy (this has already been tested in a clinicl trial) It worked for a little while for me, you might have better luck than I did. I think it's worth a try, but talk to your doctor.

[Muffin2019 in reply to mypk]

Good luck, wish you the best.

[Muffin2019 in reply to StePeteMN]

Going for my 10th one at the end of the month, most annoying is the loss of taste buds for a week and half , tiredness makes me rest, tried tripling my vitamin c and doubled the B complex but that gave me intestinal issues so will not do that again. Cheese and fat just does not work so well, feels like my mouth is coated, strange side effect.

[StePeteMN in reply to Muffin2019]

How is your hemoglobin? Are you getting Carboplatin as well?

[Muffin2019 in reply to StePeteMN]

The hemoglobin is good every time and not getting the carboplatin with it, last scan in December showed the bladder tumor is gone, the lymph and lung nodes is gone and the largest liver lesion has shrunk some but still have others on the liver. The liver functions are good, no pain, no lesions on the bone. Been careful on what to eat as to not aggravate the liver and of course no alcohol during treatment. The oncologist says doing great, if all is good I may take a break from the chemo but do not want to jeopardize the progress and will keep going with current treatment until it fails then on to plevicto . He did not say what I would take if there is a break to keep the cancer in check. I have been on Zigtea and xtandi that eventually failed in the past. My white cell count as my AB neutriphil counts recover after the three weeks before the next treatment.

[Tall_Allen in reply to mypk]

A recent trial showed that chemo can reverse Xtandi resistance:

prostatecancer.news/2022/10...

[mypk in reply to Tall_Allen]

Well..., Docetaxel can be hard stuff. It was the first therapy I got. Between the fourth and sixth infusion I often thought "If my cancer doesn't kill me, Docetaxel will". But the result was pretty good. PSA down from 1260 to 80 and less metastases activity in the bone scan.

[docbulldog in reply to mypk]

Thank you for your question. I started round 3 of chemo 3 weeks ago, Docetaxel and Carboplatin this time. My 1st lab came back with very low platelet count,34, so will not continue with infusions until that improves. My psa did drop from 758 to 611 so there was some hope. I'm wondering now if I could get back on Xtandi .

[meowlicious99 in reply to mypk]

dexa study

bjui-journals.onlinelibrary...

[mypk in reply to meowlicious99]

Thank you for the link.

Seems to be similar to the SWITCH study:

pubmed.ncbi.nlm.nih.gov/301...

[MikeMartin in reply to mypk]

Hello mypk - yes the switch worked for me

[mypk in reply to MikeMartin]

I'm currently receiving AMG-509, which is given along with 16mg Dexamethasone once per week.

[tango65]

Resistance to abiraterone could be reversed with modified niclosamide, based in preliminary data. The phase II trials at UC DAVIS finished recruitment and we are waiting for for the results.

health.ucdavis.edu/synthesi...

[StePeteMN in reply to tango65]

Keep us posted!

[Soumen79 in reply to tango65]

You have that trial number handy?

[tango65 in reply to Soumen79]

clinicaltrials.gov/ct2/show...

[anony2020 in reply to tango65]

Good info. Great link, even for those who do not need it. 😊

[Kevinski65 in reply to tango65]

I bought some of that. It's for cats. I never needed it because I'm 10 years out on xtandi and lupron.

[dhccpa in reply to Kevinski65]

Where did you buy it?

[pakb in reply to tango65]

Looks like it's been almost 5 years since that article. Wonder how it's going now?

[pakb in reply to pakb]

Just saw response below with update!

[tango65 in reply to pakb]

More recent publication

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

[reconjj in reply to tango65]

Thats very exciting news . But 3-5 yrs I might not be around .

[dhccpa in reply to tango65]

Some take niclosamide with DMSO for better absorbability, or bioavailability. Thoughts?

[tango65 in reply to dhccpa]

This modified niclosamide is a proprietary drug available only in the clinical trials. It increases the absorption of niclosamide allowing the drug to reach therapeutic levels. Regular niclosamide does not work.

[dhccpa in reply to tango65]

Yes, that's why I asked about using DMSO with it, to increase absorbability. I've never used that combo, but I read where others do for just that reason. I haven't found studies hitting that combo directly.

[exeinoo]

nature.com/articles/s41598-...

[mypk in reply to exeinoo]

Of course it will be interesting if the phase II study at the University of California Davis will demonstrate good results with their modification of Niclosamide.

They already came up with new ideas:

health.ucdavis.edu/news/hea...

The original Niclosamide doesn't establish the necessary serum concentration to work. This is due to the poor bio-availability and aqueous solubility of Niclosamide. If their phase II study (NCT02807805) is successful, I suppose the next major obstacle would be to find a sponsor for the phase III study, because in general Niclosamide is an extremely cheap drug compared to other drugs used for cancer therapies. The profit margin might be considered as too low by the drug producers.

Perhaps some day in the future somebody will also initiate a clinical study with Abiraterone Acetate or Enzalutamide plus CP-COV03, a Niclosamide modifcation being produced by Hyundai Bioscience in Korea and currently in a phase II trial for treating Covid-19 patients. They claim to have increased the bioavailability of Niclosamide up to 43 times.

[dhccpa in reply to mypk]

Have you tried niclosamide with DMSO?

[mypk in reply to dhccpa]

I didn't find any evidence that this may work. The Yomesan (Niclosamide by Bayer) Drug Information says that it's maximum serum concentration was measured between 0,2 – 6 µg/ml, which is (as far as I know) far below the required level to inhibit AR-V7 in prostate cancer cells. And the only cancer clinical trial I found in which DMSO was used, it served as an ingredient in the placebo.

See also:

pubmed.ncbi.nlm.nih.gov/298...

[dhccpa in reply to mypk]

I guess we'll have to use it in the non-placebo arm. I guess the trial already had a more bioavailable version, but that's not available.

Some swear by DMSO for bioavailability, but don't know if that theory has been tested.

[Magnus1964]

Being resistant to one ADT drug does not mean you are resistant to all ADT drugs. I was on abiraterone for over 3 years. When it failed I moved to xtandi. I was on xtandi for 4 years.

[mypk in reply to Magnus1964]

Abiraterone Acetate did work only 10 months in my case. Because usually there is a cross-resistance, I assume that Enzalutamide would work for a shorter period for me.

[Magnus1964 in reply to mypk]

Don't assume, you may be surprised. I was on casodex for 5 years. When abiraterone provided only 3 years I thought xtandi would last less than 3.

Magnus

[kayi078 in reply to Magnus1964]

So you were diagnosed in Stage 4 prostate cancer since 1992?

[Magnus1964 in reply to kayi078]

That is correct.

[Jp2sea in reply to Magnus1964]

That's great

[meowlicious99 in reply to Magnus1964]

I always think of you when someone says 'cross resistance'