Adding Zytiga Post-Chemo - necessary?

My husband was diagnosed with Stage 4 metastatic prostate cancer in February (Gleason 8, PSA not fully known - long story, but was around 20 a year ago) and has low volume disease burden. He's been on Lupron/Eligard since Feb of this year and next week is heading into the 6th of 6 chemo treatments. Now his oncologist is talking about putting him on Zytiga 4 to 6 weeks post chemo, even though his PSA has dropped to undetectable levels. I can't find any research to support adding Zytiga at this time, in this situation. Do any of you know of any research I can review that says that Zytiga this soon after chemo is a valid therapy? Thanks!

[Tall_Allen]

Zytiga after chemo is certainly a good idea. But your concern is how soon? Well, there is some suggestion that even combining them may be beneficial:

"For metastatic hormone-sensitive disease, the pooled hazard ratio (HR) for progression-free survival (PFS) was 0.63 , and the pooled HR for overall survival (OS) was 0.75 "

clinical-genitourinary-canc...

[Hidden in reply to Tall_Allen]

Thanks Tall_Allen; what's confounding is their use of the expression, "docetaxel-hormonal regimens" without clarifying which hormonal regimen. Still digging into this, but unsure if they are referring to Zytiga versus the Lupron/eligard hormone therapy which he will continue with.

[Tall_Allen in reply to Hidden]

Probably. There was a clinical trial of combining Xtandi and Docetaxel that was suspended because of the pandemic:

clinicaltrials.gov/ct2/show...

I know that Scholz combines them. What do you see as the downside to trying it soon after chemo?

[Shooter1 in reply to Tall_Allen]

I had lupron, Docetaxel and Xtandi concurrently and I am still here and in remission. PSA rose 10 pts between prostatectomy and 6 week check up. Hit it hard and was successful.

[Schwah in reply to Tall_Allen]

Yes I am a patient of Dr Scholz and I did chemo and lupron and Zytega for 21 months. I also had 3 mets that I zapped with SBRT. I’ve been off everything now for about 14 months and all my Psma imaging has remained negative. I retain 60% of a supposedly healthy prostate and my psa has stabilized at 3.5. No change in the last 120 days. I think the theory is that the chemo and the Zytega go after different prostate cancer cells so your chances of killing more of the cancer is increased by using both. If he’s on Lupron already, I don’t believe Zytega will add any substantial side effects.

Schwah

[Hidden in reply to Schwah]

Hmmm. I am under the impression that Zytiga doesn't kill cancer, but rather stops all production of remaining testosterone that is being produced by the adrenal glands and prostate.

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

Greetings,

Please tell us your husband's . Age? Location? Treatment center(s)? Doctor's name(s)? Thank You!!!

All info is voluntary, but it helps us help your husband and helps us too. If you do respond copy and paste it in his/yours home page for his/your use and for other members’ reference.

Good Luck, Good Health and Good Humor.

j-o-h-n Saturday 10/17/2020 1:12 PM DST

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

He just turned 64, and our case consultant is Dr. Singh at Mayo (Scottsdale); our local doctor is Dr. Rafiyath who coordinates with Singh, and is located at the Blood and Cancer Center here in Tucson, AZ.

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

Thank you for your QUICK and detailed response. You may wish to copy and paste your details in your husband's and your home page. Keep posting here for very good information. Keep fighting!!!

Good Luck, Good Health and Good Humor.

j-o-h-n Saturday 10/17/2020 1:27 PM DST

[Schwah in reply to Hidden]

Which in turn kills cancer cells because they have no T as fuel. Clinical studies proved that adding Zytega to lupron early on decreased deaths over 40%. And adding chemo to lupron had similar miraculous results. So logic dictates all 3 wot if he even better. I went to UCLA and asked their opinion. They said : “Makes sense and we’d like to see a study hi could firm it”.

So no proof yet on all 3. But Scholz has had great results he says with all 3 including very long term remissions that are still ongoing. It without proof you’ll need yo decide for yourself.

Schwah

[Tall_Allen in reply to Hidden]

Half right. Zytiga does kill prostate cancer cells by depriving them of all androgens (not just testosterone) from the adrenals and from intratumoral synthesis. Cancer cells require AR activation to survive.

[6357axbz in reply to Tall_Allen]

That’s good news! I’ve been under the impression that ADT, lupron, zytiga, etc., does not kill cancer, only suppresses it.

[Tall_Allen in reply to 6357axbz]

It kills susceptible cancer- not all cancer cells are susceptible.

[6357axbz in reply to Tall_Allen]

It would be nice to know how much susceptible versus non-susceptible cancer cells we have.

[Tall_Allen in reply to 6357axbz]

PSA is a fairly good marker of that in most patients. You can also look at how much tumors shrink.

[Hidden in reply to Tall_Allen]

When my husband was first diagnosed, his scans also showed a large mass in his right kidney; they thought it was a second cancer. Luckily, that tumor was benign but still required a removal of the kidney. So he started with firmagon, switched to Lupron, had his kidney removed, started chemo, switched from Lupron to Eligard... all in a matter of a months in the middle of COVID. Labs also show elevated glucose and some insulin resistance, even though he's been an Ironman athlete since the 80's. So the downside? He wants a BREAK from being hammered this year and feeling so crappy. He wants to get his fitness and energy back before they take all of his testosterone away. There's the other concern about zytiga/prednisone and its potential to flip him into full-blown insulin resistance and potentially diabetes, which could further complicate and negatively impact his long-term survival. Having one kidney to process all of these meds is a slight concern - though people say "you only need one kidney, it's a heavy load for a single kidney to manage all these harsh drugs on top of its regular duties. He has zero pain (never had any), recovers fairly well from each chemo treatment and unless there is some solid evidence that adding another drug right now to extend his life by a few months (while impacting QOL and potential blood sugar management) isn't something he's terribly keen about doing.

[Tall_Allen in reply to Hidden]

But, in general, drugs used earlier are more effective and have fewer side effects than drugs used later. Why wait until the cancer has debilitated him more so that his body is less able to cope with the side effects?

[Hidden in reply to Tall_Allen]

I don't disagree that the earlier, the better, when it comes to known treatment protocols. Taking these particular three meds at the same time isn't yet validated, and after 15 years in the health care field, I can assure you that there is no guarantee that more drugs are better, especially when there are comorbidities to manage.

While Dr. Scholz has been having success - and should we go this route, it's good to hear about his results - we don't know of those who may have gone this route and didn't fare so well. Since it's not a true trial, there are no data on adverse events, serious side effects such as insulin resistence with those who are already challenged with blood sugar management, and more. Or what percentage of his patients have been successful versus those who haven't.

Perhaps, instead, we will choose a more precision/targeted route using the University of Texas tumor profiling that we had done which shows that both metformin and statins could have a significant effect on his outcome based on his unique molecular tumor profile and pathways. Not all tumors show these benefits, but his does. It's cutting edge treatment that has been used in trials, but as our oncologist tells us, "it's not yet ready for prime time." So... either way, it's a guess.

We haven't yet determined the path forward - we have more work to do to make this decision. I'm guessing many of us are in this same boat, which is why I am deeply grateful for the various inputs from this group who have significantly more personal experience and research time under their belts. We are just beginning this journey...

Namaste.

[Tall_Allen in reply to Hidden]

But you are not talking about at the same time, you are talking about sequentially.

[Hidden in reply to Tall_Allen]

Yep, sequentially. And while chemo not administered at the same time, the effects may last a very long time.

[Tall_Allen in reply to Hidden]

Granted. So it becomes a choice of:

A) Waiting to use the hormone therapy, with known decreased efficacy and increased side effects from hormone therapy used later, or

B) Using it sooner, before full recovery from chemo is established, but with known increased efficacy and lower side effects form the hormone therapy. I would add that there is no evidence either way that hormone therapy in any way interferes with the recovery.

You don't have the results of an RCT to help you decide, so it's a judgment call. Perhaps lean on the experience of an oncologist who has done it with a number of patients?

[Hidden in reply to Tall_Allen]

Or C) explore the use of metformin along with Lupron/Eligard as an alternative to Zytiga which has been used in trials with some benefits and potentially moreso given my husband's tumor profile.

Yes, a decision that we will be facing soon. Thanks for the help!

[Tall_Allen in reply to Hidden]

That doesn't get rid of the choice between A & B. He can take metformin with whatever he decides. You're still doing option A if you put off Zytiga.

[Canoehead]

This is a personal and not scientific answer, so other results may vary. At the end of my chemo my PSA was undetectable, but I still followed it by adding Zytiga for 15 months, at which time I started an ADT vacation. Metformin will help with blood sugar while you are on ADT, and it may have other benefits. Zytiga had no additional side effects for me. Major side effect of Metformin is diarrhea. Still undetectable 18 months after stopping ADT. So I’m a true believer in the hit it hard and hit it early approach. Good luck, and the future looks bright.

[tango65]

This is en relation to the meta-analysis study :

clinical-genitourinary-canc...

posted above by TA to suggest that combining Zytiga and chemo could be beneficial.

This is the link to the full article:

sci-hub.st/https://www.clin...

Table 1 shows none of the patients in the 10 studies analyzed received Zytiga. In nine of the studies the patients received chemo and ADT . One study refers to patients receiving chemo and ketoconazole which blocks steroidogenesis and we could consider it "similar" to zytiga.