The case for Triple blockade (ADT3)

[Break60]

This blog is probably a bit dated but it’s the basis for ADT3 which my RO prescribed and supported by Dr Meyers. I don’t hear of ADT3 being mentioned here. Has it been proven to be ineffective or unnecessary?

theprostateadvocate.com/pdf...

[Tall_Allen]

This clinical trial proved it was ineffective to continue a 5-α-reductase inhibitor on intermittent ADT:

ncbi.nlm.nih.gov/pmc/articl...

[Hidden]

Hi Break60,

This helps my intermittent ADT research, I'm only on Eligard and Zytiga for 3 months, but being proactive - I'm not going to just wait around for castrate-resistant occurrence.

If T and PSA are undetectable for at least 18 months on ADT, then vacation would be reasonable IMHO..

[GP24]

Dr. Leibowitz said you could avoid surgery by using ADT3 instead. I think this did not work well and you do not want to do intermittent ADT forever instead of surgery. Here is an article by Dr. Leibowitz:

theoncologist.alphamedpress...

In there he mentions a study by Dr. Strum:

"Strum et al. have recently reported that intermittent androgen deprivation with an antiandrogen, an LHRH agonist, and finasteride (given during induction therapy and as maintenance) resulted in significantly prolonged time off intermittent androgen blockade in patients with clinically localized prostate cancer"

However, it seems that this abstract is no longer available on the net. I read that this abstract reports that the patients with finasteride did have a median break of 44 months while the patients without finasterid had 17 months without ADT.

This study reports: "Finasteride doubles the duration ...."

ncbi.nlm.nih.gov/pubmed/166...

I have a friend who does intermittent ADT3. This has significant side effects. He uses Estradiol patches to combat these. He has bone mets and believes he can kill cancer cells by pushing the PSA value to zero.

[Break60 in reply to GP24]

I’m less interested in going on IADT than I am in avoiding castrate resistance. I’ve employed IADT3 for nearly five years and am still hormone sensitive. But I’ve had mets since 2015 which I’ve radiated and my vacations have been too short to make much of a difference in quality of life.

My interest is in driving PSA to zero and my question is should I stay on ADT3? My profile summarized my history. I’ve already had RP and lots of RT . I’m only on LHRHa and xgeva ( plus metformin, Crestor, celecoxib and estradiol patches) PSA is down to .4 and T is 9. I don’t see any downside to resuming casodex and dutasteride. But with T already so low I wonder if there’s any need to push it down further.

[pjoshea13 in reply to GP24]

Odd that the 1999 paper is not in PubMed. But I found the Abstract elsewhere:

"Scholz M, Strum S, McDermed J: Intermittent androgen deprivation (IAD) with finasteride (F) during induction and maintenance permits prolonged time off IAD in localized prostate cancer (LPC). J Urol 161:156A, 1999.

"INTRODUCTION AND OBJECTIVES: To determine if F significantly adds to the effectiveness of IAD, we examined patient (pt)- and treatment-specific factors in hormone-naive pts with LPC who elected to discontinue IAD.

"METHODS: All pts received IAD, 32 with a luteinizing-hormone releasing-hormone agonist (LHRH-A) + an antiandrogen (AA) and 27 with an LHRI-I-A, AA + F (10mg/d). Those receiving F in induction continued F as maintenance while off lAD. All pts achieved and maintained an undetectable (UD) PSA (<0.05ng/mL) on lAD and were assessable off CHB for ≥ 12 months (mo).

"RESULTS: Clinical stages were PSA relapse (PSAR, 25pts), T1c (8pts), T2a-c (26pts). During induction, F-treated pts had a shorter time to reach UD-PSA v pts not on F (mean 3.6 v 4.9mo, p=0.0095). After lAD was stopped, F-treated pts had a similar testosterone recovery (mean 4.I v 6.7mo, p=0.10), but a slower PSA velocity v pts not on F (mean 1.43 v 5.25ng/ml/year, p=0.00013). Time to PSA=2.5ng/ml for F-treated pts and 5.0ng/ml for pts not on F were:

... see link for graph ...

"CONCLUSIONS: With a median follow-up of 36mo (range 17+ to 70mo), only 5/27 F-treated pts restarted IAD. F maintenance significantly extends time off lAD by significantly slowing PSA velocity despite testosterone recovery"

researchgate.net/publicatio...

-Patrick

[GP24 in reply to pjoshea13]

Thank you, Patrick, for this link!

[Break60 in reply to pjoshea13]

Patrick:

That's nice but I don't have localized PCa. Never really did. I don't reckon that gleason 9 is ever localized or if so, not for long.

[GP24]

I believe castrate resistance can be avoided for an extended period by reducing the tumor burden with radiation and surgery. Fewer tumor cells mean fewer resistant tumor cells and fewer cells which can mutate to resistant cells. But this is just what I believe.

My friend is impressed by Dr. Myers. He has extensive knowledge regarding PCa. He believes to push the PSA value to zero is a good recommendation by Dr. Myers. However, there are no trials which prove a benefit for that. But he lives for 10 years with bone mets now and is not castrate resistant yet.

[Break60 in reply to GP24]

GP24

Well I’ve kicked the hell out of tumor burden!

I’ve had low volume oligomets which is a big plus.

I haven’t found the SEs from ADT3 to be all that bad but I dropped casodex and dutasteride to see what it did to reduce SEs. I really think metformin, celecoxib , Crestor and estradiol patches have helped keep my gl9 at bay. All Dr Meyers recommendations.

Ten years for your friend is spectacular! I hope for the same.

Bob

[GP24 in reply to Break60]

In this small study they observed an extended period to castration resistance when combining local therapy with ADT in oligometastatic PCa:

onlinelibrary.wiley.com/doi...

up.picr.de/34893265hz.png

MDRT = metastasis directed radio therapy

[j-o-h-n]

BTW how's the fishing going?

Good Luck, Good Health and Good Humor.

j-o-h-n Monday 01/21/2019 1:02 AM EST

[Hidden]

I'm new to HealthUnlocked, is there information somewhere on what you refer to as ADT 1, ADT 2, ADT 3, 4,5, and 6? TIA

[Break60 in reply to Hidden]

Just read the link I posted.

[GP24 in reply to Break60]

The article does not mention ADT 4, 5 and 6.

@Indyflyer: ADT1 is Lupron and alternatives, ADT2 is the combination of Lupron and Casodex, ADT3 is the combination of Lupron, Casodex and Finasteride/Dutasteride. ADT3 is intended as intermittent ADT and the Finasteride or Dutasteride shall be continued when Lupron/Casodex is stopped to provide a longer break.

[Break60 in reply to GP24]

I know but that’s Nalakrat’s own concoction. I think it’s in his reply but you might ask for clarification.

[Break60 in reply to GP24]

GP24

So you're saying or implying that ADT3 is not meant for guys who can't take a break? Is that because of the side effects? I must say that I was told to use ADT3 for 13 months only and that's what I've done, twice now in 2015 and 2017. Unfortunately when I stop Lupron (or trelstar) but remain on casodex and dutasteride, my PSA quickly climbs, doubling in two months. Then I have Pet CT scans when PSA is between 1 and 2 , find bone mets, zap them with SBRT and go back on Lupron and PSA quickly declines. This time I've stopped casodex and dutasteride to see what happens and PSA still declined rapidly.

[GP24 in reply to Break60]

"So you're saying or implying that ADT3 is not meant for guys who can't take a break? " I tried to say the opposite:

"ADT3 is intended as intermittent ADT"

Just if you make a ADT holiday, you should continue with Finasteride or Dutasteride. Dr. Strum expects this will result in a longer holiday. See the study Patrick found.

Frankly, if you have a doubling of two months, you should try to get a PSMA therapy. There is good logic behind ADT3 but no good evidence yet. It may be not effective enough for you.

[Break60 in reply to GP24]

GP24

What is a PSMA therapy?

[GP24 in reply to Break60]

It is discussed as PSMA Lu177 therapy in this forum. Or see this list of Allan's blog entries:

pcnrv.blogspot.com/search?q...

[Break60]

Nal

Thanks. My RO ,Dr Dattoli, who treated Dr Meyers fully subscribes to the triple blockade theory. It seems intuitive that attacking T from every direction makes sense. I can’t argue with the results I’ve had with my Gleason 9 stage pt3b PCa. I just haven’t been able to have long adt vacations due to fast PSA doubling time.

Bob

[j-o-h-n]

"the weather is to be great".

And we're freezing our asses off here in NYC (5 degrees this morning)...

Enjoy...

Good Luck, Good Health and Good Humor.

j-o-h-n Monday 01/21/2019 11:59 AM EST

[Break60]

if there was a way to slow down my PSADT I sure as hell would try it!!

[GP24 in reply to Break60]

See this trial:

ncbi.nlm.nih.gov/pubmed/305...

However, you should look for mets with a PSMA PET/CT since that locates more mets than a bone scan.

[Break60 in reply to GP24]

GO24

Yes that’s what I used last time and prior to that, axumin. My profile is very clear on what I’ve done.

Bob

[j-o-h-n]

You know the difference between a Yankee and a damned Yankee?

A Yankee visits, a damned Yankee stays.

I know I worked for 6 months as a consultant for the First Citizens Bank in Raleigh... But the boss works here in NYC and she's the boss...and the boss is the boss... and of course I can't give up NYC water bagels.....

Good Luck, Good Health and Good Humor.

j-o-h-n Monday 01/21/2019 5:31 PM EST

[j-o-h-n]

I heard from good sources that the guy who owns the place is Joey Buttafuoco.

Good Luck, Good Health and Good Humor.

j-o-h-n Monday 01/21/2019 10:17 PM EST

[j-o-h-n]

ha ha ha touché you got me there....

Good Luck, Good Health and Good Humor.

j-o-h-n Tuesday 01/22/2019 12:21 PM EST