Double Dosing

[miina]

There have been a few posts about the illogic of continuing with preliminary ADT ie Zolodex when taking a supplemental such as Zytiga or Erleada. The latter are supposed to provide total androgen annihilation. I know that all trials included both.Any recent thoughts on the subject as one less drug would be great

[GP24]

This was tested in this small trial:

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

I would like to add that Zoladex has no side effects, only the lack of testosterone causes these. So you can expect that the side effects will be no different if you stop Zoladex and just continue with Zytiga and Prednisolone.

[pjoshea13 in reply to GP24]

This is from something I wrote in April:

"There was a concern that Abiraterone [Abi] as monotherapy, by reducing testosterone [T] levels, induces a 3-4 times increase in luteinizing hormone [LH]. I haven't read anything to suggest that this is an actual problem, but I don't know what the %-effectiveness is of Abi for suppressing T of gonadal origin. Perhaps the addition of classic ADT leads to a more complete gonadal suppression? ..."

***

In any event, one can easily experiment. Continue with ADT-basic initially & get a full hormone panel after a few months. Drop ADT-basic & repeat the test after a few months. Compare panels & report back.

Some would only test T, but Dr. Myers felt that DHT was more important. Why test for DHEA-S, etc? I'd be interested in anything the cancer might be able to use.

-Patrick"

[GP24 in reply to pjoshea13]

Here are two slides from a presentation of the Spare trial:

up.picr.de/36938034ql.png

The table at the top shows that Abiraterone without Lupron reduces the testosterone level just as much as the combination Abi with Lupron (Arm A): 0.029 ng/ml or 0.1 nmol/L.

The lower part shows the LH-levels during the trial. As you expected, the LH-levels did increase without Lupron. The red bar shows the normal level, so the LH-levels increased more than that. However, Abiraterone reduced the testosterone levels in spite of high LH-levels.

Abiraterone is an inhibitor of the CYP17A1 enzyme. The body cannot generate testosterone without the CYP17A1 enzyme. Therefore Abiraterone inhibits androgen biosynthesis not only within the testes but also in the adrenal glands and the tumor microenvironment, e.g. the tumor cells.

Here is the study protocol: ncbi.nlm.nih.gov/pmc/articl...

[podsart in reply to pjoshea13]

Has anyone compared the triple action and type of impact of Xtandi on AR versus Zytiga impact on the cypa1a pathway in terms of effective and durable results?

[tom67inMA]

I suspect part of the reasoning, though I've never heard it explicitly stated, is that the primary ADT is there as a backup if for some reason you miss a dose of the second line hormonal (forgetfulness, delayed in shipment, have to stop due to liver issues, insurance paperwork, etc., etc.)

Trial based evidence is sorely lacking, with only the SPARE trial linked by GP24 that I'm aware of. Interesting thing in that trial is the group without primary ADT did insgnificantly better! But it was a small trial with old men who didn't live long.

[GP24]

The trial which was done to get the FDA approval had a control group which did ADT and the other group did ADT plus Abi. So the FDA approved ADT plus Abi and since then all patients have to take ADT plus Abi. The manufacturer has no interest to finance another trial comparing ADT versus Abi without ADT.

If, as Tom pointed out, maybe 30% of the patients in the trial did not take their pills as instructed, the trial may have shown no benefit for Abi without ADT and this expensive trial would have been unsuccessful.

[pjoshea13]

I should point out that while there is redundancy when Zytiga (Abiraterone, Abi) is added to basic-ADT (Zoladex, Lupron, etc), the same is not true for Erleada (Apalutamide) or any of the other androgen receptor [AR] antagonists.

-Patrick

[GP24 in reply to pjoshea13]

I hope the EMBARK trial will be successful. Then you can take the AR antagonist Enzalutamide/ Xtandi without Lupron. Since the testosterone is not reduced, this will cause less side effects.

[Tall_Allen]

Erleada does not provide "androgen annihilation" although Zytiga might. Erleada acts only on the androgen receptor (AR), blocking it, and does nothing to stop production of androgens by the testes or the adrenals. In fact, serum testosterone and other androgens will increase if one takes only an antiandrogen. That may not be a problem early on, but as the AR mutates, the excess serum androgens may become problematic.

Erleada seemed to not add to the side effects of a GnRH agonist (like Zoladex) in a recent trial.

Zytiga alone seemed to be as effective as Zytiga + a GnRH agonist in one small trial. Not enough to hang one's hat on.

[Fairwind]

Besides, Lupron et-al generate some nice reimbursements. The Oncologists and the Urologists are not going to give that up unless they have to...Lets not forget, for most of us, it's only a matter of time before all of this this stuff quits working..

[Ron53]

Much of the above is beyond my comprehension, but when I went undetectable after having been on Lupron for 1 year and Zytiga for 6 months of that 1 year, I ask doctor let me stop for a while. He said he just couldn’t recommend it. I said then let me skip the Lupron shot and keep taking Zytiga, so he agreed to that. It’s only been 2 months and can’t say there is much change in the side effects. Hot flashes are fewer...down from every 30 minutes to about every hour. They seem more intense when I get one, but may just be because there are fewer of them. I believe I read here that it takes months for the side effects to wear off and I really don’t know what side effects remain with just taking Zytiga. Maybe some here knows. Next doctor visit in November, I’m going to quiz him hard about stopping the Zytiga as well for 3 months. I just want to see if the cancer is in some state of hibernation. Won’t know unless I try and see. Hopefully that won’t make it ineffective if PSA goes back up. Feel like I gotta try and see.

[mcp1941 in reply to Ron53]

While on Z+P It took 2 months to get to undetectable and stayed there for 9 months. Side effects of Z was was so bad ( excruciating leg cramps ) that I asked MO if I could Z. He said to stop Z and also Lupron. Stopped all ADT and went on a two year holiday. The first nine months of the holiday PSA remained undetectable then it began a slow rise. T took some time to return and never rose above lower reference range. but enough for me to see progress at the gym. Man, that was a GREAT 2 years.

[TEBozo]

Lam of Prostate Oncology Specialists in Marina del Rey has me on Firmagon and Zytiga/prednisolone simultaneously for 18 month for Firmagon and 12 months for latter. Localized lymph node involvement after RP and IMRT. They are shooting for a "cure" and dont want me to treat my PC as a chronic disease.