Zytiga resistance and Chemo

[Dani2861]

Hi everyone,

After 16 months on Zytiga (which started shortly after a failed RP in Jan 2018), my father's PSA jumped from 4 in June to 19 in August to 55 last week. A genetic test showed he has a T878A alteration in his AR gene, which I believe means he is mcrpc and resistant to abiraterone. His doctor is starting him on taxotere on Sept 29th. I'm wondering if anyone is aware of any cross resistance that may impact the efficacy of chemo? I know chemo has been life saving for many people here, especially those who received it early, but I'm not sure about its efficacy in those who have progressed while on Zytiga and I'm seeing some mixed information online. We are very concerned about the side effects of chemo and want to make sure we are making the right decision to go with chemo at what seems to be a late stage of the disease.

They also found a C675 alteration in BRCA1 so are checking to see if this will qualify him for clinical trial for PARP inhibitors (if anyone has information on this alteration that would be most welcome as well) . In any event the MO says he has to go through chemo first before any clinical trial as he's never had it.

Thank you all very much. I'm an only child living on the other side of the world from my father, so it has been quite a lonely experience and this forum has provided invaluable advice and moral support.

[NPfisherman]

Dani,

You and Dad are in a tough place, but never lose hope....

Some information from Dr Evan Yu--Darolutamide-- shown in preclinical trials to be effective against t878a:

urotoday.com/clinical-trial...

You could look at getting it "off label" use ....

Another thought would be the ARV-110 clinical trial...An AR degrader that looks promising...

Finally, consider VERU-111 if docetaxel does not work....In clinical trials, it is an alpha and beta tubulin inhibitor --I believe it is an oral formulation and supposedly tolerated well...

Other posters will be along with more ideas I am sure...

In about a year or so, we should see the following vaccine trial which I posted on previously...

healthunlocked.com/advanced...

May God grant you and Dad wisdom and strength in your fight with APC....

Best of luck...

Don Pescado

[Lupronzytiga in reply to NPfisherman]

Amen

[Dani2861 in reply to NPfisherman]

Thank you, I had not heard of VERU-111 so will definitely ask our MO about it. I’m also hoping xofigo, ac225 and LU 177 are options down the line but need to discuss with the MO as he hasn’t mentioned.

[tango65]

He could also be treated with olaparib or similar. The Toparp B study showed a positive response in 83% of patients with BRCA defects:

urotoday.com/conference-hig...

There are several clinical trials using olaparib:

clinicaltrials.gov/ct2/resu...

You could consider the clinical trials at Davis using modified niclosamide which could resensitize the cancer to abiraterone (Zytiga) or enzalutamide:

clinicaltrials.gov/ct2/resu...

health.ucdavis.edu/synthesi...

urotoday.com/conference-hig...

There is not a definitive agreement about the right sequence of drugs to treat metastatic prostate cancer. There is some "evidence" that the sequence of one anti androgen and then chemo when the anti androgen fails could be more effective than using another anti androgen..

ncbi.nlm.nih.gov/pubmed/302...

[Dani2861 in reply to tango65]

thanks, the Davis trial sounds really interesting. We were also told the chemo might resensitize the cancer to Abiraterone but not sure how often that actually is.

[tango65 in reply to Dani2861]

You are welcome. Best of luck

[Tall_Allen]

The side effects of chemo are worse the longer you wait. It is possible that chemo may reverse this mutation as it has been found to sometimes for AR-V7. There seems to be a therapeutic overlap between carboplatin and PARP1 inhibitor. MD Anderson is running a trial of cabazitaxel+carboplatin followed by a PARP inhibitor.

clinicaltrials.gov/ct2/show...

Here are some clinical trials he may qualify for:

pcnrv.blogspot.com/2018/02/...

[Dani2861 in reply to Tall_Allen]

Thanks so much, I think his doctor is checking if he can qualify for the Triton trial. Still a bit unclear if the specific BRCA1 alteration qualifies him for the trial or whether it’s a VUS.

[tango65]

Discuss with your doctor the negative effects of olaparib and of chemo particularly when using carboplatin and docetaxel

about-cancer.cancerresearch...

google.com/url?sa=i&source=...

[paulcross4]

I did 8 cycles of Docetaxel/Carboplatin after Zytiga failed (8 months). The efficacy of the chemo was great and side effects tolerable. There was no reason to believe the Zytiga had impacted the chemo at all

[Dani2861 in reply to paulcross4]

That’s great to hear!

[j-o-h-n]

Where are you located and where is your DAD located?

Good Luck, Good Health and Good Humor.

j-o-h-n Thursday 09/19/2019 5:33 PM DST

[Dani2861 in reply to j-o-h-n]

I’m in Brooklyn and he’s in Israel.. not ideal!

[j-o-h-n in reply to Dani2861]

That's one hell of a commute.... Shalom to you both.....

Good Luck, Good Health and Good Humor.

j-o-h-n Thursday 09/19/2019 6:00 PM DST

[scarlino]

After Zytiga failed for me (18 months) I went on taxotere. Side effects were tolerable. Unfortunately that failed as well. Now on Jevtana . 3 cycles in my PSA is decreasing. Chemo side effects are pretty individual. I pray your dad’s are not too bad.