question about iADT or BAT

[TheTopBanana]

Hello! I’ve searched this forum and articles for information about iADT or BAT and I’m wondering if anyone wants to share their personal experience? My father is Gleason 9 oligometastatic. I’m very grateful for Patrick/Pjoshea13 telling me about his history with BAT and it got me very curious about the possibily of iADT or BAT as a possibily for my father to stay HS. Also if you know any oncologists in Scandinavia who have expertice in this, I understand that BAT is rarely SOC until someone is CR. Thankful for any thoughts!

[Magnus1964]

The protocol for iADT (intermittent androgen deprivation theraphy) is one that is used when a particular drug begins to fail. It is a last chance to extend the efficacy of the drug. I am not a fan of iADT for any other reason.

I can not speak about BAT. I have not been exposed to it.

[TheTopBanana in reply to Magnus1964]

Thank you very much for your reply!! If you wish to elaborate: how come you are not a fan?

[Magnus1964 in reply to TheTopBanana]

I don't have a problem with iADT if the drug you are on begins to fail. However, I have heard of some doctors who try it sooner than necessary. I have others call this the "ADT vacation". I believe this only gives a new line of cancer cells a chance to become resistant to the drug.

[Tall_Allen]

BAT is experimental. It is not standard of care for anyone.

iADT is probably not a good idea in men who are oligometastatic. It may lower survival.

[TheTopBanana in reply to Tall_Allen]

Now I'm confused, in this post healthunlocked.com/advanced... you replied:

"Intermittent is still an option, and maybe with oligometastatic SBRT it may be good. But the treatment will make all the traditional PSA benchmarks for vacations useless and I'm not sure how iADT would work without PSA. Same for BAT."

[Tall_Allen in reply to TheTopBanana]

It is an option, but it may or may not be a very good one. There is no data on using metastasis-directed therapy (MDT) with iADT. If your father can't stand ADT and needs a break at all costs, then that is what he will do. Hussain found that for men with minimal metastases, the median survival was 5.4 years in the intermittent-therapy group, as compared with 6.9 years in the continuous-therapy group . Will MDT change that? who knows? And how will he set the vacation times?

[TheTopBanana in reply to Tall_Allen]

I understand the potential downsides now, but then I don’t understand the potential positive sides? When you wrote ”maybe with oligometastatic SBRT it may be good” did you only mean good if he would have bad symtoms from ADT in the future of only that no one knows if it positive or negative to combine MDT and iADT?

[Tall_Allen in reply to TheTopBanana]

I meant that the only reason to use iADT is to get a vacation from ADT side effects. Yes, no one knows if iADT is positive or negative when combined with MDT of oligometastases. I can develop plausible arguments pro and con - only a clinical trial can provide that info.

[noahware]

I cannot share any personal experience, but happy to share some findings. This article explores the issue a bit:

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

Importantly, "simply discontinuing ADT and allowing androgen recovery to a eugonadal state does not appear to enhance survival; studies of intermittent androgen suppression in metastatic disease, which also allows gradual T recovery to physiological levels, demonstrated a trend toward inferior survival compared to continuous ADT." [I will add, that trend did NOT appear to be an overwhelming one.]

Further, "the paradoxical inhibitory response of PCa to supraphysiological androgens has been demonstrated in multiple in vitro and in vivo studies. Several groups have reproducibly demonstrated a biphasic proliferative response to androgen... [Meaning in some studies VERY low T levels inhibits PC progression, "normal" ranges of low to high T levels will support progression, and then VERY high supraphysiological T levels once again inhibit PC progression.]

And "despite compelling preclinical evidence that the androgen-repressive effect is often magnified in CR tumor variants, clinical observations do not necessarily support this. In the early studies of Fowler and Whitmore 45 of 52 men had unfavorable responses to exogenous T, and the proportion of men who had an unfavorable response was higher in those who had been on prolonged hormone suppression (94%) compared to castration-naïve men (25%), or men in early stages of hormone suppression (36%)." [This seems to be a primary study on which it was concluded that TRT or BAT would very likely prove harmful to some men, but paradoxically BAT is now most commonly pursued AFTER castrate-resistance rather than BEFORE even though it seems the earlier approach might give better outcomes... and I suspect this has a lot to do with the reluctance to stray from established consensus standards of care.]

[TheTopBanana in reply to noahware]

Thank you very much! I will read this thoroughly!

[TheTopBanana in reply to noahware]

I just copy pasted this to his doctor. I will definitely look into it!

[DarkEnergy]

Intermittent androgen deprivation therapy (iADT) sounded great when I first heard about it after my PCa diagnosis. But, then reality settled in, someone with my situation: PSA 1000+, diagnosed with a tumor growing out from the prostate gland and invading the bladder wall. With extensive metastasis around pelvic and vertebrae. Moreover, symptoms of horrible pain and burning sensation when urination with blood.

In less than a week with just Casodex, the symptoms subsided! After 6 months of Lupron, Zometa and Zytiga, PSA <0.02, to date...

So, should I try iADT?

Obviously, my PCa is hormone sensitive, can't imagine there's any upsides to iADT. Also, how long does it take for testosterone to recover from castration levels?

[noahware in reply to DarkEnergy]

For some, the biggest potential upside to iADT is improved QoL, assuming no return of any symptoms. Another possible upside would be a lengthening of time to castrate-resistance, although there is some debate over whether that really happens very often.

That leads into your last question, as to T recovery. Research suggests that some men would do better with rapid supraphysiological T than with slow natural T recovery (BAT instead of iADT) since there is evidence of biphasic responses to T, as noted in my comment above.

[RICH22 in reply to DarkEnergy]

Another casodex success story. thnx.

[Easey]

I had my Bat experience very recently. I was expecting my psa to rise after the first injection and that's what happened. My oncologist sent me for a CT scan before he would give me the go ahead for injection # 2. Unfortunately the tumors had grown and now appears to have also spread to my ribs. I was very optimistic about having the treatment but "shit happens"

[Big_Mcc in reply to Easey]

Thk u 4 posting. My QoL is miserable and I was planning to ask my Dr for BAT. However miserable my life is Im not ready to die yet. Will push forward against the pain and depression until I cant.

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

It sure does..........

Good Luck, Good Health and Good Humor.

j-o-h-n Monday 08/03/2020 9:55AM DST

[Horse12888]

My MO, David Quinn at USC, is an extremely senior practitioner in this field. He prescribes IADT for the rest of my life when my PSADT goes under 10 months.

Now it's possible that his choice here is based on his experience with me the first time around, where he had prescribed 24 mos as an adjuvant to IMRT after my RP had left positive margins and a post-op G4+5=9. I was so miserable that I quit after 12 mos. He may be offering IADT as a carrot to get me on board.

Yet I'm loath to try this. I'm worried that the vacations aren't going to be long enough to be worthwhile, and that this experience is going to be even worse, because it means a lifetime of misery with no hope. That's what hit me so hard the first time, the pounding relentlessness.

BAT sounds like a real option, though. I really couldn't care less if it's not the SoC.

[immunity1]

Here is a recent 2020 ASCO abstract re a study highlighting the value of BAT BEFORE Enzalutamide as compared to Enza alone, or reversed sequence, for CRPC patients having had abiraterone.

5517

Background: Rapid cycling between high and low testosterone (T) (i.e BAT) produces tumor response in mCRPC, and may overcome resistance to newer AR therapies. Here we report a randomized study comparing BAT to E in men with mCRPC progressing on abiraterone (A).

Methods: In this phase 2 trial, men received either T cypionate 400mg IM (BAT) once every 28 days or daily oral E 160mg. Primary endpoint was clinical/radiographic PFS; crossover was permitted at progression. Secondary endpoints were OS, PSA progression to primary and crossover therapy, PSA and objective responses (OR), time to PSA progression from randomization through crossover (PFS2), quality of life (QoL), and AEs. Results: 195 men were randomized (94 to BAT, 101 to E).

Results are presented in table. Although diametrically opposed therapies, median PFS and PSA response in the intent-to-treat (ITT) population was not significantly different between BAT and E. OR and OS favored BAT. For those who received BAT and then crossed over to E the PSA50 response was 77.8% and time to PSA progression was 10.9 mo compared to 25.3% and 3.8 mo for those receiving E immediately after A. The sequence of treatment had a significant effect on median PSF2 which was 28.2 mo for men receiving BAT→E vs. 19.6 m for E→BAT. For men who crossed over from BAT to E, OS was 37.3 mo vs. 28.6 months for those receiving E without crossover. AEs were primarily grade 1-2 in the BAT arm and included fatigue, generalized pain, and lower extremity edema. BAT improved QoL (fatigue, physical functioning, sexual function) vs. E.

Conclusions: BAT could be safely administered to asymptomatic men with mCRPC. BAT produced a comparable PFS to E in A-refractory mCRPC pts. However, PSA50 and OR after crossover, as well as PFS2, were significantly improved in men who received BAT→E versus E→BAT. OS in men receiving BAT→E was 37.3 mo, exceeding historical expectations. These results support the hypothesis that treatment with BAT is safe, has efficacy and can restore sensitivity to antiandrogens. Clinical trial information: NCT02286921.

[TheTopBanana in reply to immunity1]

Thank you!

[Easey]

You can quote BAT statistics until the cow's come home. After 1 ! injection my metastasis grew ( lung, liver and rib)

I had Enza before BAT , asymptomatic healthy and fit. Conclusion : BAT can backfire

[kaptank in reply to Easey]

It is well documented that the first BAT injection will cause a PSA flare but I have no info on whether it also increases mets. The Demneade group at Johns Hopkins say that they try to go for 3 months of BAT before concluding failure or success. If enza was still in your system, it may interfere with BAT by blocking the PCa access to the supra T. I stop my androgen blocker (bicalutamide) for a month to clear my system before injecting . However I can find nothing in the literature on this, I am simply assuming that having BAT while a strong androgen blocker is still in the body is counter productive, they work against each other.

I found the most prominent effect of BAT was to resensitise the PCa to the androgen blocker rather than any direct effect of supra T on PCa.

[TheTopBanana in reply to Easey]

I’m sorry to hear that you had such a horrible experience with BAT! Thank you for sharing.

[Easey]

I'm hanging on to your last paragraph and will probably revisit Enza and BAT at some stage if I get another chance. I was told to stop Xtandi a week before and the MO was confident that the wash out would be fine. As it happened, I stopped about 10 days before so this could have been a factor ? Who knows, I was hoping to go at least a few cycles with it. I had a CT scan before the injection and again 28 days later which showed clinical progression.