Neither of my two Medical Oncologists on board with early Zytiga after early chemo

Just to add to your quandary..

There is some (scant) evidence (6 of 14 patients) that chemo can sometimes re-sensitize the cancer to Zytiga:

/academic.oup.com/annonc/article/26/9/1859/189846/Serial-blood-based-analysis-of-AR-V7-in-men-with

Johns Hopkins is conducting the "RESTORE" clinical trial to see if supra-physiologic alternating doses of testosterone can restore sensitivity:

/clinicaltrials.gov/ct2/show/NCT02090114

And, as I said, some trials combine chemo and advanced hormonals at the same time.

So there are lots of sequencing possibilities, and no clear answers yet

Starfinder,

I've thought about this issue a lot. We are paying out of pocket for Zytiga so it wasn't an easy decision. I'm not sure if my theories are correct, but here they are.

1. There seems to be some kind of synergistic benefit for ADT + Zytiga or Chemo for hormone sensitive men. If you wait to add Zytiga (or chemo) to the castrate-resistant setting, you'll lose that synergy.

2. Slow/stop progression now, worry about future later. Even if there is an argument that it was best to save Zytiga for the future, if it can slow/stop progression now, then who knows what drugs might be out in 3 years. Rapid advancements are being made.

3. Easier to fight the cancer early on, when there is less of it and no or fewer mutations.

We'd do chemo too but uro says no, not without identifiable mets. We were offered a neoadjuvant clinical trial of Zytiga, ADT and chemo all combined. It might have been the best thing for my husband but his PSA had begun to rise on neoadjuvant Firmagon and uro said if cancer progresses primary treatment might not be available. We couldn't risk it.

The plan now it 2 yrs Firmagon + Zytiga (post aRT). I hope that my husband is not castrate resistant then.

Here are a couple of very recent short videos discussion the issue
/www.youtube.com/watch?v=RjZcZfxyuuo
/www.youtube.com/watch?v=pHa9fYhncjg

I have been on Firmagon and Casodex Bicalutamide) (for 2 1/2 years now with a PSA of <0.02. I mentioned Zytiga do my Dr. last week and he wondered why I would want to rock the boat after having such an excellent response (above average) he said on the current regiment. He left it up to me so now I am very confused

Starfinder,

In answer to your questions:

I think primary treatment might not be offered if my husband progressed to develop visible mets because the benefit of this treatment is not evidence based with a phase 3 study and the government in Canada won't pay.

Chemo is more beneficial for guys with mets. My husband has none that we know of.

Starfinder-

While there is no data on sequencing of early chemo and Zytiga, there is data on chemo and Zytiga sequencing among men with mCRPC .

These retrospective analysis found that the order did not make a difference in terms of overall survival:
meetinglibrary.asco.org/record/140488/abstract
onlinelibrary.wiley.com/doi/10.1002/pros.23064/abstract

This looked at docetaxel followed by abiraterone:
/link.springer.com/article/10.1007%2Fs00345-014-1375-5

These looked at abiraterone followed by docetaxel:
onlinelibrary.wiley.com/doi/10.1002/pros.22872/abstract
www.clinical-genitourinary-cancer.com/article/S1558-7673(14)00059-7/fulltext

There have been a few pilot studies combining them, and they found that toxicity was acceptable enough to expand to larger scale clinical trials , which are ongoing. e.g,:
www.europeanurology.com/article/S0302-2838(16)00130-5/fulltext
/academic.oup.com/annonc/article/28/1/90/2676854/Phase-I-II-trial-of-cabazitaxel-plus-abiraterone

I haven't seen any reports of excessive toxicity due to the sequencing or the simultaneous use in men with mCRPC. Because they tend to be sicker/more vulnerable than men with mHSPC, I wouldn't expect that your doctor's concern would be a major one, but close monitoring is certainly appropriate.

>cardiac or hepatic issues...
>I'm going to try to get a source for this if possible...

Hi Gregg,

In the Prescribing Information for Zytiga the areas of Hepatic and Cardiac issues and Adverse Reactions are reported and discussed in Sections 2.2, 5.3, and 6.1 of this recent version of the document.

/www.zytiga.com/shared/product/zytiga/zytiga-prescribing-information.pdf

Charles

Tall Allen said...
I haven't seen any reports of excessive toxicity due to the sequencing or the simultaneous use in men with mCRPC. Because they tend to be sicker/more vulnerable than men with mHSPC, I wouldn't expect that your doctor's concern would be a major one, but close monitoring is certainly appropriate.

I agree, looks like the risk is fairly low.

The issue I have at this point is that I now have 3 doctors telling me not to go on Zytiga mainly because it hasn't been proven that there is an additional survival benefit to doing Zytiga early after chemo vs doing it later at CRPC.

TA, speaking of Darolutamide (ODM-201). So far it's showing some promise.

It's too bad the ARASENS trial is only accepting patients with no previous treatment. If they had a trial for CRPC patients it could probably be fast-tracked if the trial was successful.

Who knows how long it will be until FDA approval.

Here's quote from an article I read:

"One advantage is that darolutamide has been found to block the activity of all tested/well-known mutant ARs in prostate cancer, including the recently identified clinically-relevant F876L mutation that produces resistance to enzalutamide and apalutamide."

That's a bummer. I'll have to hold out that long so it will be available

I've just e-mailed my Kaiser doctor who was at an ASCO presentation Q & A regarding the STAMPEDE trial. I asked her if there is any way to get a transcript of that. I'll post if I can provide a source.