In need of advise for my father

[AerospaceElectrical]

Hello everyone. My father was diagnosed with metastatic stage 4 PCa in another country (2017). He immediately had bi-lateral orchiectomy, and thereafter when the PSA began to rise, he was prescribed Xtandi (lasted ~6 months) and subsequently had some radiotherapy to the pelvis and spine (pain management).

The pain returned and the MO suggested Docetaxel. He had 6 rounds of Docetaxel and the PSA did not go down much, in fact the PCa progressed. The MO then suggested Cabazitaxel, and after a few rounds, it was stopped because the treatment was ineffective.

What next treatment might be best for my father at this point? He is going to have an area treated with radiation to get rid of the pain in the coming days. He has not had Provenge, Zytiga, Lu-177 (is only under trials here in the United States), Xofigo, Cytoxan, BAT (was informed my father has mutations that qualify him for testosterone trials).

[AerospaceElectrical]

He has the TP53, CCND1&2, RB1 R661W, CCNE1, and several AR mutations.

I doubt that he has the mutations suited for PARP inhibitors to work.

[noahware]

If it was me, I would opt for BAT (if possible) from the list of possible therapies. Dr. Denmeade has said (I think) that a drastic change in hormonal regime may be more important for some cancers than a mere deprivation of hormone, which we already know can lead to work-arounds by the cancer cells.

According to Dr. Denmeade, there are three phases of androgen inhibition: shock, adaptation, and resistance. The concept of cycling and introducing a new "shock" as a way of dealing with resistance seems so logical, and is consistent with observations by Huggins decades ago that hormonal cancers might be influenced either by hormonal deprivation (our current SOC of castration only) or by "hormonal interference" (which could mean EITHER high doses of estrogen OR high doses of T).

This high-T is also riskier, because there is very little clinical data to back it up as anything close to a sure thing. Possibly it could increase pain. All the options are gambles, but this even more so. But to me, seems a sensible one.

If appropriate and not already done, some lifestyle changes to diet and exercise might help, too.

[AerospaceElectrical in reply to noahware]

I modified his diet (he's vegan), and he is not really able to exercise as much as he used to. He has been on perpetual hormone therapy since having the bi-lateral orchiectomy.

I concur with your sentiment regarding opting for BAT. We consulted with Denmeade, and he stated that BAT could be tried once my father is pain free from having radiotherapy.

[Tall_Allen]

I think you've covered all the bases of known therapies. You mentioned "mutations" so I assume he already had a genomic test that found little that was actionable (Was an AR mutation found that qualified him for BAT?).

Provenge combined with Xofigo was found to be a synergistic combination in a recent small trial.

What country is he in? Lu-177-PSMA is available per protocol in several countries.

[AerospaceElectrical in reply to Tall_Allen]

We are in the United States.

Dr .Denmeade mentioned during the consultation we had with him that my father had 2 mutations (he has a few AR mutations) that would qualify him for testosterone trials. I forgot to ask of him which mutations they were. If I recall correctly, Dr. Denmeade might have stated that one of the mutations was TP53. Again, I might be mistaken.

I did not know that Provenge could be combined with Xofigo. I did read that it is being combined with Xtandi, I think.

Can someone have Xofigo after having photon radiotherapy for bony pain?

Another question Tall Allen, one of my father's oncologists wants him to try Zytiga with Prednisone since he already had Xtandi followed with Docetaxel and Cabazitaxel. Do you think this is prudent approach?

[Tall_Allen]

I know JH is very thorough about genomic analysis. Maybe pursue discussions with Denmeade for his BAT trial? I know it is risky, but they monitor him very closely, and Denmeade has been trying to isolate why it works well for some patients but not for others. If Denmeade thinks it might benefit your father, I think it's worth considering. Here's some info you may find useful:

pcnrv.blogspot.com/2016/09/...

He can certainly still have Xofigo after the very localized spot radiation he had. In fact, bone pain is one of the indications for it. Here is the small trial combining Xofigo and Provenge.

ascopubs.org/doi/abs/10.120...

There is an ongoing RCT combining Xofigo and Xtandi. As you may know, they stopped the RCT combining Xofigo and Zytiga because of excess fractures. They are using a bone-preserving agent (Xgeva or Zometa) on everyone in the Xofigo+Xtandi trial. Whether that will be enough is anyone's guess at this point. Although Xgeva/Zometa reduced the fracture rate, there were still some excess fractures in the Xofigo+Zytiga trial.

Sometimes (maybe a third of cases) chemo can reverse resistance to Xtandi/Zytiga, so Zytiga is worth trying.

[AerospaceElectrical in reply to Tall_Allen]

Would a medical oncologist be able to concurrently give a patient Xofigo and Provenge treatments? Or is it only permitted in trials?

[Tall_Allen in reply to AerospaceElectrical]

There is no blackbox warning (as there is for Xofigo+Zytiga) so they can be prescribed simultaneously. My friend just did that, in fact.

[AerospaceElectrical in reply to Tall_Allen]

I've read that Xofigo can be tough on the blood count. Are the side effects that adverse?

A fellow member mentioned Nubeqa. What do you think of Nubeqa? It's not prescribed for metastatic CR PCa like Zytiga.

I noticed yesterday that my father has some swollen lymph nodes in his chest that is now visible & painful above his top ribs. Can that area be radiated or only a systemic treatment can work? Your thoughts?

[Tall_Allen in reply to AerospaceElectrical]

Quite the opposite- Xofigo is usually devoid of significant side effects. Grade 3/4 thrombocytopenia occurred in just 6% radium-223 patients vs 2% of placebo patients.However, when cancer has progressed so there are pre-existing hematologic problems, side effects can be more significant. As you see below,

clinical-genitourinary-canc...

As you said, Nubiqa is not indicated for mCRPC - so why the question?

Radiation up there can have very serious side effects on vital organs. You have to consult with an RO about using it palliatively. If systemic therapy (chemo, hormones, Lu-177-PSMA) doesn't help, I don't know what can be done short of surgical dissection.

[Hidden]

I've read that a new anti-androgen Darolutamide (Nubeqa) was shown to be effective against AR mutations.

In the US it's currently approved for non-metastatic castrate resistant PCa, but doctors are prescribing it for some metastatic patients that can't tolerate the side effects of Xtandi.

That or Zytiga might be worth a try.

Everything else has been mentioned so I won't repeat the other options.

[AerospaceElectrical in reply to Hidden]

Thanks much for the feedback gregg57. Somehow, I am just hearing about this medication.

[Hidden in reply to AerospaceElectrical]

Here's more info about Darolutamide.

accessdata.fda.gov/drugsatf...

[j-o-h-n]

How old is your Dad? Current location? Thank you!

Good Luck, Good Health and Good Humor.

j-o-h-n Sunday 05/24/2020 11:41 PM DST

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

My father will be 75 next month. We are located in Washington DC.

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

Thank you for your reply. 3/4 of a century for Dad....Give him my regards and tell him he's got another 1/4 to go...(he'll make it, if you get him out of D.C.).....

Good Luck, Good Health and Good Humor.

j-o-h-n Monday 05/25/2020 11:04 AM DST

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

Thanks much for your kind message. May I enquire why getting him out of D.C. would increase his lifespan? LOL

[honolu]

The urologist and RO were scheduling me for Proton Radiation Therapy. I requested ct, pt, bone & mri scans before proceeding. All scans can back negative results for nodes or lesions and the urologist and RO couldn't explain to me why they were pushing me to LU-77 and radiation. I didn't take radiation, changed urologist and have been on a holistic/integrative protocol. Even with no indications the oncologist said he would apply radiation in five locations because he doesn't believe in the holistic protocol.

[AerospaceElectrical in reply to honolu]

Hey honolu. Do you mind mentioning what the 5 locations are that the RO wants to radiate?

[honolu]

they were areas of my abdomen below my navel.