Estrogen and Androgen Blockade for Advanced PCa.

[pjoshea13]

New paper below [1].

Something of a curiosity, since many continue to deny that estrogen can be involved in PCa.

Some may recall that I recommend a low-dose estradiol [E2] patch for bone health, if ADT brings E2 under 12 pg/mL - so a complete E2 blockade isn't a good idea. However:

"Recently, estrogen and androgen blockade (EAB) using a combination of toremifene and ADT has been demonstrated to improve biochemical recurrence rate in treatment-naïve bone metastatic PC."

Toremifene "is a selective estrogen receptor modulator (SERM) and hence is a mixed agonist–antagonist of the estrogen receptor (ER), the biological target of estrogens like estradiol. It has estrogenic effects in bone, the liver, and the uterus and antiestrogenic effects in the breasts." [2]

... & seemingly, the prostate.

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/293...

Cancers (Basel). 2018 Jan 23;10(2). pii: E29. doi: 10.3390/cancers10020029.

Estrogen and Androgen Blockade for Advanced Prostate Cancer in the Era of Precision Medicine.

Fujimura T1, Takayama K2, Takahashi S3, Inoue S4.

Author information

1

Department of Urology, National Center for Global Health and Medicine, Tokyo 162-8655, Japan. [e-mail].

2

Department of Functional Biogerontology, Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0015, Japan. [e-mail].

3

Department of Urology, Nihon University School of Medicine, Tokyo 173-8610, Japan. [e-mail].

4

Department of Functional Biogerontology, Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0015, Japan. [e-mail].

Abstract

Androgen deprivation therapy (ADT) has been widely prescribed for patients with advanced prostate cancer (PC) to control key signaling pathways via androgen receptor (AR) and AR-collaborative transcriptional factors; however, PC gradually acquires a lethal phenotype and results in castration-resistant PC (CRPC) during ADT. Therefore, new therapeutic strategies are required in clinical practice. In addition, ARs; estrogen receptors (ERs; ERα and ERβ); and estrogen-related receptors (ERRs; ERRα, ERRβ, and ERRγ) have been reported to be involved in the development or regulation of PC. Recent investigations have revealed the role of associated molecules, such as KLF5, FOXO1, PDGFA, VEGF-A, WNT5A, TGFβ1, and micro-RNA 135a of PC, via ERs and ERRs. Selective ER modulators (SERMs) have been developed. Recently, estrogen and androgen blockade (EAB) using a combination of toremifene and ADT has been demonstrated to improve biochemical recurrence rate in treatment-naïve bone metastatic PC. In the future, the suitability of ADT alone or EAB for individuals may be evaluated by making clinical decisions on the basis of information obtained from RT-PCR, gene-panel, or liquid biopsy to create a "personalized medicine" or "precision medicine". In this review, we summarize ER and ERR signaling pathways, molecular diagnosis, and SERMs as candidates for advanced PC treatment.

KEYWORDS:

androgen deprivation therapy (ADT); androgen receptor; estrogen-related receptor; personalized medicine; precision medicine; prostate cancer; selective estrogen receptor modulators (SERMs); stem cell

PMID: 29360794 DOI: 10.3390/cancers10020029

...

[2] en.wikipedia.org/wiki/Torem...

[EdBar]

Interesting, I have been using Estradiol patches since 2015 per Dr. Myers to relieve ADT SE's and to help rebuild sclerotic areas on my skeleton due to treated metastatic PCa. It is my understanding that they are also an effective form of treatment. Now that I am seeing Dr. Sartor since Snuffys retirement I continue to use a patch daily, keeping 2 patches on at a time. I also continue to use triple HT - Xtandi, Lupron and Avodart just as I have for 3+ years now. PSA undetectable for 3 years now and scans show no active disease. Hopefully this continues, meanwhile if it works don't fix it.

cancernetwork.com/prostate-...

Ed

[GeorgeGlass in reply to EdBar]

Have you used ADT such as Lupron?

[EdBar in reply to GeorgeGlass]

Since day 1 along with Casodex later Xtandi and avodart

[GeorgeGlass in reply to EdBar]

thanks Ed, I'm only on Lupron. Have studies shown that adding casodex and Avodart increases survivability, or is it an unstudied hypothesis? My MO doesn't support it but I like to research on my own. When did you start the ADT/Lupron?

George

[EdBar in reply to GeorgeGlass]

I started Lupron and Casodex on day 1 of dx, later added Avodart per Snuffy Myers. I guess it depends on your situation - whether you’re metastatic or not. I was Stage 4 with mets to spine, pelvis, ribs, sternum and several nodes. If you are metastatic then early chemo and/or Xtandi has been shown to have a positive impact on OS.

[GeorgeGlass in reply to EdBar]

They think Im metastatic but haven't seen the mets on SoC scans. They are leery of zytiga because I have Coronary Artery Disease so I'll probably use Xtandi next but my MO likes to add treatments as failures begin, as opposed to combining them up front.

[Hidden]

Erik Castle talked about toremifene three or four years ago. His comment on toremifene is that it had a narrow therputic window. He was working with another SERM raloxifene. But I am interested in the article because it mentions the alpha and the beta receptors.

audio-digest.org/adfwebcast...

I have the audio of this talk abstracted above. (Its on audio digest) [paywall]

But here is a more reccent publication on "the same" topic.

I have not read it yet. Just found it while looking for a video of the above talk.

pdfs.semanticscholar.org/eb...

[Hidden in reply to Hidden]

But he has been quiet since then.

Now he is pushing robotic surgery at Mayo/Arizona. ??

[GeorgeGlass in reply to Hidden]

what is the narrowness of the therapeutic window?

[GeorgeGlass]

Patrick, here is a summary of a very small study, showing effectiveness of Toremifene used in addition to ADT. bmccancer.biomedcentral.com...

I stumbled upon AC protein expression when reading about radiation induced prostate cancer and decided to read up on AC. I found this: ncbi.nlm.nih.gov/pubmed/239...

I haven't heard much about this topic except from talking to Nalakrats about avoiding estrogen because high levels are found in people who have died from PCx. What are the recent thoughts/studies showing about adding Toremifene to Lupron and overall survival rates?

Anyone else on this thread, your comments are welcome too.

thx,

George