Intermittent HT, does it prolong HTs effectiveness

[alephnull]

I asked this on another forum and only got a yes it does.

What I'd really like is, are there studies that show this?

[GP24]

In my opinion it depends on the tumor burden. If you have a lower burden you can choose intermittent ADT.

The studies I know show a slight advantage for continuous ADT. You have to ask yourself if you prefer QOL and take a little risk for that. Here are the studies I refer to:

nejm.org/doi/full/10.1056/N...

nejm.org/doi/full/10.1056/N...

[charlesmeyers1964 in reply to GP24]

what is A.D.T.?

[GP24 in reply to charlesmeyers1964]

I you do not know that you are not advanced

en.wikipedia.org/wiki/Andro...

[Shooter1]

Interesting study, but for us with metatastic cancer at diagnosis, looks like constant ADT for life or Orchiectomy are the only viable options.

[alephnull in reply to Shooter1]

I am confirmed to lymph nodes so I'm metastatic. I have a spot on my lung that is too small to biopsy. But my Onco has me on intermittent. I was thinking to have an orchiectomy but that would mean no more vacations from therapy (HT).

So that is the context I'm asking from.

[Shooter1 in reply to alephnull]

Gleason 9/10 with lymph nodes and bone mets. Not candidate for IADT from the start. Good luck to you with any lower Gleason scores.

[GP24 in reply to alephnull]

"I am confirmed to lymph nodes so I'm metastatic."

Sometimes pelvic mets are considered "positive nodes" and not mets. If you make that destinction you are metastatic if you have bone mets or lymph node mets outside the pelvis.

Just mets in the pelvis I think are a low burden and you can do intermittent ADT.

A PSMA PET/CT would tell you if the spot on your lung is cancer.

[charlesmeyers1964 in reply to alephnull]

THAT DOES NOT MUCH FROM YOUR CANCER. READ ABOUT IT AND U WILL FINE A BRIEF LOWER OF ones psa but it then goes up so keep your balls it really doesn't make much of a defense.

charlie

[pjoshea13]

When I was diagnosed 14 years ago, it seemed that there was resistance to intermittent ADT [IADT]. The feeling was that survival had to be worse than continuous ADT. & that IADT was inappropriate if there were mets.

The IADT promoters argued that improvements in QoL outweighed a small reduction in survival time. Ultimately, the feeling seems to be that IADT is non-inferior - but offers no advantage except improved QoL.

From a 2012 Finnish paper [1]:

"A total of 852 men with advanced prostate cancer (PCa) were enrolled to receive goserelin acetate 3.6 mg every 28 d for 24 wk. A total of 554 patients whose prostate-specific antigen (PSA) decreased to <10 ng/ml or by ≥50% (<20 ng/ml at baseline) were randomised to IAD or CAD {continuous ADT}."

"In the IAD arm, ADT was resumed for at least 24 wk whenever PSA increased >20 ng/ml or above baseline."

"IAD showed benefits in the treatment of advanced PCa with respect to QoL."

In a 2014 follow-up [2]:

"Median follow-up time was 65 months. Median times from randomization to progression, death, prostate cancer death and treatment failure in M0 and M1 patients were" given, &:

"No significant differences emerged between IAD and CAD. ADT showed a beneficial effect on pain, activity limitation and social functioning in M1 patients, and a deleterious effect on physical capacity in M0 patients and on sexual functioning in both groups. IAD offered extra benefit for activity limitation, social functioning and recovery of sexual functioning."

"IAD is as efficient as CAD in treatment of locally advanced and metastatic prostate cancer. ADT improves quality of life in M1 patients, with IAD offering extra benefit."

From a 2014 review [3]:

"Androgen deprivation therapy (ADT) has been the standard of care for metastatic prostate cancer for decades; however, the choice of continuous or intermittent administration is a matter of debate. Two large phase III trials have reported results comparing these 2 forms of ADT administration. The National Cancer Institute of Canada (NCIC) PR-7 trial studied men with an increasing prostate-specific antigen (PSA) level and no evidence of metastatic disease after definitive or salvage radiation therapy and radical prostatectomy. The Southwest Oncology Group 9346 trial studied men with newly diagnosed hormone-sensitive metastatic disease. The primary end point in both trials was overall survival with a noninferiority design. The NCIC trial showed that the overall survival in men treated with intermittent ADT was not inferior to that of men treated with continuous ADT, but the SWOG trial was inconclusive regarding noninferiority. Certain domains of quality of life were better in the intermittent arms of both trials. If using ADT in the setting of biochemical relapse, intermittent ADT should be strongly considered over continuous ADT, except perhaps in patients with Gleason score of 8 or higher. In men with metastatic disease, continuous ADT remains the standard of care, because the SWOG trial did not establish noninferiority of intermittent ADT with respect to survival. However, for those with significant side effects from ADT, establishing the risk group, as determined by PSA value after 7 months of ADT or the presence of pain at diagnosis, may help guide the choice of intermittent versus continuous ADT in men with metastatic disease."

You might be interested in a series of vlog posts by Dr. Myers. His aim with IADT was to prolong the off-phase of IADT, since patients typically only enjoyed 3 cycles before CRPC. The posts were actually concerned with durable remissions. Myers claims that this can't be done with a single agent.

I haven't time to track down all his posts, but here's one on the role of Metformin in a durable remission:

askdrmyers.wordpress.com/20...

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/228...

[2] ncbi.nlm.nih.gov/pubmed/246...

[3] ncbi.nlm.nih.gov/pubmed/248...

[alephnull in reply to pjoshea13]

Thanks pjoshea13

[Tall_Allen]

The question you should be asking is whether there is a survival benefit to iHT. For men with metastases (M1), the Hussain study showed that iHT MAY be iNFERIOR to continuous,but it was inconclusive. They further showed that continuous is superior in men with a low metastatic burden.

nejm.org/doi/full/10.1056/N...

Other comparative studies that included recurrent and locally advanced patients, found no difference in survival. There have been MANY trials, and there are meta-analyses done (below) that come to the same conclusion.

ncbi.nlm.nih.gov/pubmed/224...

meetinglibrary.asco.org/rec...

eusupplements.europeanurolo...

bmcurol.biomedcentral.com/a...

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

The decision of iADT vs cADT is NOT about whether iADT puts off CRPC and thereby increases survival, it is purely about the breaks one gets from hot flashes and loss of libido. Most studies show, however, that the patient evaluated QOL is similar over time.

[alephnull in reply to Tall_Allen]

Thanks TA!!

[mklc in reply to Tall_Allen]

Good morning TA and Happy New Year to you and your family,

Is an aggressive doubling time (2 months dblg time) an important factor in deciding if you should go continuous ADT versus intermittent?

Your opinion is appreciated.

Sincere thanks.

Lynn

[Tall_Allen in reply to mklc]

No - the decision should be based on potential quality of life improvements alone.

[mklc in reply to Tall_Allen]

This is a tough one because I know he should be on continuous ADT.

But as you said, there is the QOL.

Thank you for your straightforward opinion.

Best wishes to you and yours

[dockam]

I took a hormone holiday after 30 months of ADT (Lupron & Casodex). Last shot on 03/31/2017 and now at 10.2 PSA from 840 at Dx in 01/2015. Mets to L ureter lymph nodes. 15 chemos in 2015. Did 150mg Casodex/day during holiday. T got to 1002. Time will tell if it worked, but I really enjoyed my QoL for 1 year and 1/2.

Fight On

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

Of course you enjoyed your Qol, you live in Hawaii..

Aloha.

Good Luck, Good Health and Good Humor.

j-o-h-n Wednesday 12/19/2018 10:54 PM EST

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

Haha, I go home to Hawaii twice a year to see family. I live in SoCal

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

Oh! In that case I'll visit with them the other two times....

Good Luck, Good Health and Good Humor.

j-o-h-n Wednesday 12/19/2018 11:32 PM EST

[charlesmeyers1964]

what is ht?

[alephnull in reply to charlesmeyers1964]

Hormone therapy or ADT - Androgen Deprivation Therapy, Lupron, Eligard,...etc

[Hidden]

My view is based on going intermittent not because of any study. I wanted a QOL break and was going to return to treatment when my PSA showed the need. I was able to go six months and I felt like it was worth the risk. My oncologist did not tell not to he was supportive with caution. I had PSA tests every week. When my numbers went up I had the Auxumin PET so we could see where I was with cancer growth. That was also worth the break for me. Do what you want we get one life to live and make a decision for you. We offer advice on our experiences but we are all different too so what works for me may be not the best for you or could be better than my results.

Who knows?

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

God does, but He/She? ain't telling.

Good Luck, Good Health and Good Humor.

j-o-h-n Wednesday 12/19/2018 10:57 PM EST

[Break60]

I have low tumor burden with Gleason 9 . Have used IADT plus RT since 2014 to good effect when oligomets popped up. . Now I’m just on trelstar but have used metformin continuously since 2015 . When on ADT holiday, I get scans when Psa rises to about 2.0 then go back on ADT and zap mets with SBRT.