Diethylstilbestrol when faced with "economic constraint".

[pjoshea13]

New study below [1].

We see so many posts on Zytiga, Xtandi & even more expensive drugs. This study is from Lahore, Pakistan & reports on DES [Diethylstilbestrol] use in CRPC cases.

"All patients were treated with DES (2.5 mg) initially, but the dose was increased for some patients to 5 mg in combination with aspirin (75 mg)."

I do not presently have CRPC - I use 1 mg DES, which I view as a low-dose (some manage on less) as part of my home-grown BAT regimen. 5 mg or higher was common in the old days. So 2.5 mg is an intermediate dose.

"A total of 91 patients were included in the study, and the mean patient age was 66 ± 8 years. The median baseline PSA was 150 ng/mL (range: 56-626 ng/mL), and the median Gleason's score was eight. A total of 90.1% of patients had metastatic disease at the time of diagnosis."

Pretty much what one would expect in a population with a low level of screening. i.e. those destined for advanced PCa were mostly already there at diagnosis.

"the median time to PSA progression was 597 days" after orchiectomy or LHRH analog. Just short of 20 months.

"After DES treatment was started, 78 patients (87.7%) showed a PSA response, and median time to progression was 212 days. In 24 patients (26.4%), the PSA response was maintained for more than a year. The PSA response was quantified as a good response (i.e., ≥50% PSA drop) or as a partial response (i.e., <50% PSA drop). The good PSA response was observed in 56 patients (61.5%) with a median time to progression of 273 days, and 22 patients (24.2%) had a partial response maintained for 109 days. Thirteen patients (14.3%) did not respond to DES treatment.

"DES is an effective, economical, and relatively safe drug in patients with CRPC."

DES is a synthetic estrogen which was used for ADT for decades. I have known two men with a great response to DES without a drop in testosterone [T]. Both maintain high T levels & low (near zero) PSA. I wish I knew the secret.

But it's clear from the response in CRPC cases that DES does more than cause castrate T levels. Something to consider.

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/312...

Cureus. 2019 Apr 16;11(4):e4470. doi: 10.7759/cureus.4470.

Diethylstilbestrol in the Treatment of Castration-resistant Prostate Cancer: A Lower-middle-income Country Experience.

Ali A1, Khalil MAI1, Khan N1, Abu Bakar M2, Amjad A3, Ahmed I4, Mir K1.

Author information

1

Surgical Oncology, Shaukat Khanum Memorial Cancer Hospital and Research Center, Lahore, PAK.

2

Biostatistics and Epidemiology, Shaukat Khanum Memorial Cancer Hospital and Research Center, Lahore, PAK.

3

Surgery, Shaukat Khanum Memorial Cancer Hospital and Research Center, Lahore, PAK.

4

Urology, Shaukat Khanum Memorial Cancer Hospital and Research Center, Lahore, PAK.

Abstract

INTRODUCTION:

Prostate cancer is the second most common cancer and the fifth leading cause of death worldwide. Its metastatic stage is associated with considerable morbidity and may lead to death. In Pakistan, given the high levels of economic constraint, patients with castration-resistant metastatic prostate cancer can be treated with cost-effective medications like diethylstilbestrol (DES).

OBJECTIVES:

The goal of this study was to assess the efficacy and adverse effects of DES when used in patients with castration-resistant prostate cancer (CRPC).

MATERIALS AND METHODS:

From January 2011 to December 2016, all medical records of patients with a diagnosis of prostate cancer resistant to the effects of castration presenting at Shaukat Khanum Cancer Hospital and Research Centre, Lahore, were reviewed. All patients were treated with DES (2.5 mg) initially, but the dose was increased for some patients to 5 mg in combination with aspirin (75 mg). The patients were followed clinically with prostate-specific antigen (PSA) value assessment. The PSA response to treatment, time to disease progression, and adverse events were recorded and analyzed using IBM SPSS Statistics for Windows, Version 20.0 (IBM Corp., Armonk, NY).

RESULTS:

A total of 91 patients were included in the study, and the mean patient age was 66 ± 8 years. The median baseline PSA was 150 ng/mL (range: 56-626 ng/mL), and the median Gleason's score was eight. A total of 90.1% of patients had metastatic disease at the time of diagnosis. Hormonal ablation was provided with bilateral orchiectomy for 71 patients (78.0%), and luteinizing hormone-releasing hormone (LHRH) analog was provided for 20 patients (22.0%). With this treatment, the median time to PSA progression was 597 days. After DES treatment was started, 78 patients (87.7%) showed a PSA response, and median time to progression was 212 days. In 24 patients (26.4%), the PSA response was maintained for more than a year. The PSA response was quantified as a good response (i.e., ≥50% PSA drop) or as a partial response (i.e., <50% PSA drop). The good PSA response was observed in 56 patients (61.5%) with a median time to progression of 273 days, and 22 patients (24.2%) had a partial response maintained for 109 days. Thirteen patients (14.3%) did not respond to DES treatment. The median percent change in PSA was -55.52% (range: -99.9 to +422). Thromboembolic complication was observed in eight patients (8.7%) patients while two patients suffered from liver toxicity.

CONCLUSION:

DES is an effective, economical, and relatively safe drug in patients with CRPC.

KEYWORDS:

castrate resistant prostate cancer; diethylstilbestrol

PMID: 31249748 PMCID: PMC6579324 DOI: 10.7759/cureus.4470

[GP24]

Here is another study that looks at DES in CRPC:

ncbi.nlm.nih.gov/pubmed/242...

[Ralph1966]

Hi,

You mentioned "home-grown BAT regimen"

What type of plants is this?

If it is a plant then where to get the seeds?

[gusgold in reply to Ralph1966]

He calls it the Gator Blood Plant and a small packet of seeds is $150,000

[Ralph1966 in reply to gusgold]

J-o-h-n where are you?

Please help, your friend is here again.

Do something LOL....

Humor is good...

[monte1111 in reply to Ralph1966]

I think you need BATMAN

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

For best results... plant it between the kale and the pot....

Good Luck, Good Health and Good Humor.

j-o-h-n Monday 07/01/2019 11:00 PM DST

[George71]

Are you saying DES does not knock out testosterone like ADT or block testosterone like casodex?

[pjoshea13 in reply to George71]

George,

DES blocks T production in the same way as estradiol [E2] does. But it is synthetic & a very small percentage of men do not respond to it in that way.

-Patrick

[George71 in reply to pjoshea13]

If DES is similar to E2 patches but more likely to cause blood clots -- why not just go with E2 patches instead?

[pjoshea13 in reply to George71]

George,

Note that the post is about DES being effective after ADT has failed. Only 14.3% of CRPC cases did not respond.

When E2 used as ADT fails, DES might work, but when Lupron fails, I doubt that E2 would be useful.

-Patrick

[George71 in reply to pjoshea13]

I see, so shouldn't they take a blood thinner if clotting is a higher risk?

[pjoshea13 in reply to George71]

Warfarin, which I believe is still the most common anticoagulant, is never prescribed prophylactically - it is considered to be too dangerous.

My view is that nattokinase &/or aspirin + D-dimer testing is better than anticoagulation, which may cause a bleed-out if one is involved in an accident.

-Patrick

[gusgold]

Pat,

I read a paper where DES has a chemo like effect on the PCa cells...that might explain why it can work on crPCa. I bought a 5 gram bottle.....what is amazing is how small 1 mg actually is. I bought a microgram spoon rather than invest in a scale. The 5gm bottle will last 5000 days

Gus

[pjoshea13 in reply to gusgold]

Gus,

You did well - none of the compounding pharmacies around here can get hold of the powder.

I don't know what "a microgram spoon" is. Hopefully, it will give you 5,000 scoops.

-Patrick

[curious-mind1]

Thanks, Pat for sharing this. It seems like once Zytiga fails, DES can be taken to continue restricting the cancer from growing. Do we know if it possible to use DES as part of an ADT regimen, say with Zytiga and Lupron and Avodart?

Arthur

[pjoshea13 in reply to curious-mind1]

DES was the standard before Lupron. The reason for shifting to Lupron was that the 5 mg dose of oral DES came with a significant risk of a blood clot.

"Orchiectomy or DES or both were the standard initial treatment for symptomatic advanced prostate cancer for over 40 years, until the GnRH agonist leuprorelin was found to have efficacy similar to DES without estrogenic effects and was approved in 1985." [1]

After 21 days on 1 mg DES, my breasts tell me that the dose is working. The risk of a clot is small at that dose, but a D-dimer [2] test & nattokinase eliminates that risk IMO. Neither were around before 1985.

So, yes, you could use DES as part of an ADT regimen - but hold the Lupron. I imagine that there would be considerable resistance from your doctor. Very few doctors in practice who remember the DES era.

(Until Medicare put an end to it, doctors were getting ~$1,000 for giving the Lupron shot. DES & Lupron may have similar efficacy, but DES prescriptions were not going to pay for that vacation home. LOL)

-Patrick

[1] en.wikipedia.org/wiki/Dieth...

[2] en.wikipedia.org/wiki/D-dimer

[j-o-h-n]

Diethylstilbestrol, Thank you, another great word for my Scrabble group.

Good Luck, Good Health and Good Humor.

j-o-h-n Monday 07/01/2019 11:05 PM DST

[Fuzzman77]

I talked with the compounding pharmacy that I got DES 1mg from about 3 or 4 years ago. They are mostly a pet pharmacy and do not make DES for humans anymore. The lady I talked to agreed with me it was too cheap of a drug and that is why human use was discontinued. Geesh. On the other hand vet can write one for Fido, and they will make it for Fido. It was only like $30.00 a month or so. Way too cheap I guess. Wedgewood.pet for the vets among us. At least it is out there. My guess I could easily get it in India for a few bucks when I go soon for treatment.