Hormone Refractory Question...

New Topic Post Reply Printable Version
[ << Previous Thread | Next Thread >> ]

gibson00
Regular Member


Date Joined Nov 2009
Total Posts : 212
   Posted 8/20/2010 1:16 PM (GMT -6)   
When saying PCA has become Hormone Refractory...
Does that mean that the ADT is no longer working and your body has testosterone in it, or does it mean you still don't have testosterone, but the cancer is growing anyway?

The reason I ask, the thread today (or yesterday) about the DES treatment.......when I read up on that treatment, it basically sounds like another form of ADT, in that it wipes out the testosterone, no? So how does DES help if you still have no test in your body anyway?
Father 65 y/o at diagnosis November 2009
Gleason 9 & 10, stage 3 - seminal vesicle involvement
Two TURPs mid Nov. 2009
Foley Catheter
Casodex for last two weeks of November '09, then Lupron.
Suprapubic Catheter March 18th, but blocked right away, back to Foley...
Started IMRT March 25th, Chemo on hold due to catheter bleeding issues, etc.
Ended IMRT and Chemo (Taxotere) late May
Mid-July - pain finally better controlled with Fentanyl patch
Late July - Superpubic Cath. removed, peeing normal again
July 21 - PSA .21

zufus
Veteran Member


Date Joined Dec 2008
Total Posts : 3149
   Posted 8/20/2010 3:29 PM (GMT -6)   
Good question is it complicated to some degree I can refer you to Journal of Urology Article and you can learn about it alot more. PCa cells have receptors on the cells, oddly enough regardless of 'T' level you have, these cells take in (accept) the DES (estrogenic drugs of various types) and can cause direct apoptosis (direct kill)..says so in Journal Article. Does it kill them all???, that is actually either a no answer or unknown to some degree, in select patients maybe (there exists an old Journal Article-relating to anectdotal cure-but is not in the psa era so maybe it wasn't definable, sure looked good anyway). There are cases of patients using such drugs (mostly blasts from the past), that lived so long they died from other ailments not PCa related (one by a poster on this forum-a grandfather). This was used for decades as front line treatment not just hrpca patients and worked well other than the overdosing with 5-mg and no aspirin or blood thinners...those caused the negatives...other wise was very useful and still is, 1-mg found safe per Journal Article. Note unlike LHRH or casodex....No hot flashes, no sweating, they say no bone density loss or memory loss...it has much different mechanisms at work. On bones it talks about osteoclasts and osteoblasts...read in article to comprehend, it is much different and  doesn't ruin your bones. (gee no doc mentioned these things or the drug probably). I found that 1/2 mg likely will work too. Technically I don't see why one couldn't use this drug at any level of PCa,  doesn't have to be 2nd line or towards final line, although docs using such put this as 2nd line therapies. So where are the abstracts in low or med. risk patients??? (no money zone???)

Unlike LHRH this can work on cells that become resistant to Lupron etc and casodex, whereby you have a rising psa level and likely your 'T' was increasing and was the cause for the psa level increases, monitored of course. There is a rare exception (like usual) in PCa whereby very aggressive types give off no psa, low number doesn' always mean safe, onco-docs monitor various markers and other tests to determine what is going on in such patients. Estrogenics could still be useful even in those highly aggressive situations, I have witnessed such in a couple patients, the bad news is the duration could be alot shorter or even lousy. Some of those rare very aggressive or variant PCa's don't respond well to about anything, but they are very rare...and very worrisome. Tried to answer  this stuff not sure it is clear. Someone else may have something to say on it, besides bashing it based upon non-useage and not reading the Journal Article.

ttp://ffyates.com/prostate/des.pdf     (Journal of Urology, Nov. 2003)
 
(only the messenger, if you don't like the message, find other targets :-) )
Dx-2002 total urinary blockage, bPsa 46.6 12/12 biopsies all loaded 75-95% vol.; Gleasons scores 7,8,9's (2-sets), gland size 35 normal, ct and bone scans appearing clear- ADT3 5 months prior to radiations neutron/photon 2-machines, cont'd. ADT3, quit after 2 yrs. switched to DES 1-mg, off for 1 yr., controlled so well, resumed, using intermittently, pleased with results

Post Edited (zufus) : 8/20/2010 2:57:41 PM (GMT-6)


tarhoosier
Regular Member


Date Joined Mar 2010
Total Posts : 495
   Posted 8/20/2010 3:53 PM (GMT -6)   
Hormone refractory means that the cancer cells have become super efficient at dividing even in a very low testosterone environment. Even the small amount of other male hormones and the intra-cell production of testosterone from cholesterol is sufficient to drive cell division. Cholesterol is very close to testosterone (and estrogen) and can be made into T in such conditions, even in the cell itself. Thus the depletion of T is insufficient to cause cell death of the PCa cells. Estrogen compounds work in a slightly different way (see above) and can provide more cell death for some time in such conditions. Eventually nearly all patients must move to more toxic treatments.

compiler
Veteran Member


Date Joined Nov 2009
Total Posts : 7269
   Posted 8/20/2010 5:10 PM (GMT -6)   
Zufus:
 
Something I always wondered about in HRPCA:
 
Do the cancer cells start out getting killed by the HT and then mutate and become resistant? Or are there a very small number of cells that are HRPCA from the start. In this scenario, as the other cancer cells die, these cells keep multiplying and eventually are the noticeable ones.
 
Mel
PSA-- 3/08--2.90; 8/09--4.01; 11/09--4.19 (PSAf: 24%), PCA3 =75 .
Biopsy 11/30/09. Gleason 4+3. Stage: T1C. Current Age: 64
Surgery: Dr. Menon @Ford Hospital, 1/26/10.
Pathology Report: G 4+3. Nodes: Clear. PNI: yes. SVI: No. EPE: yes. Pos. Margin: Yes-- focal-- 1 spot .5mm. 100% continent by 3/10. ED- in progress. First post-op PSA on 3/10/10-: 0.01. PSA on 6/21/10--0.02. Next PSA late Sept.

John T
Veteran Member


Date Joined Nov 2008
Total Posts : 4268
   Posted 8/20/2010 6:18 PM (GMT -6)   
In some patients there are a small amount of cells that are hormone refractory. The success of HT is dependent on the ratio of androgent dependent cells to androgen independent cells. Ht will kill all of the adrogen dependent cells and that's why some patients go into completete remission. The remaining independent cells will grow and mutate, adapting to the various drugs. Depending on how many cells remain depends on how fast the cancer grows.
There is a free DVD set on the PCRI website by Dr Sholtz and Dr Lam talking about hormone refractory PC.
JT

64 years old.

PSA rising for 10 years to 40, free psa 10-15. Had 5 urologists, 12 biopsies and MRIS all neg. Doctors DXed BPH and continue to get biopsies yearly. 13th biopsy positive in 10-08, 2 cores of 25, G6 less than 5%. Scheduled for surgery as recommended by Urological Oncologist.

2nd Opinion from Dr Sholtz, a Prostate Oncologist, said DX wrong, pathology shows indolant cancer, but psa history indicates large cancer or metastasis. Futher tests and Color Doppler confirmed large transition zone tumor that 13 biopsies and MRIS missed. G7, 4+3, approx 16mmX18mm.

Combidex MRI in Holland eliminated lymphnode mets. Casodex and Proscar reduced psa to 0.6 and prostate from 60mm to 32mm. Changed diet, no meat and dairy. All staging tests indicate that tumor is local and non agressive. (PAP, PCA3, MRIS, Color Doppler, Combidex, tumor reaction to diet and Casodex, and tumor location in transition zone). Surgery a poor option because tumor is located next to the urethea and positive margin is very likely; permanent incontenance is also high probability with surgery.

Seed implants on 5-19-09, 3 hours door to door, no pain, minor side affects are frequency and urgency; very controlable with Flowmax and lasted 4 weeks. Daily activities resumed day after implants with no restrictions. Gold markers implanted with seeds to guide IMRT.

25 treatments of IMRT 6 weeks after seed implants. No side affects at all.

PSA at end of treatment 0.02 mostly the result of Casodex. When I stop Casodex next week expect PSA to rise. Next PSA in November. Treatments and side affects have greatly exceeded my expectations. Glad to have this 11 year journey finally conclude.

JohnT


zufus
Veteran Member


Date Joined Dec 2008
Total Posts : 3149
   Posted 8/20/2010 8:01 PM (GMT -6)   
Thanks John, looks like a great answer and decently said, you have been really busy on PCa analysis in totality on all fronts. You have put more time into studying up than me and probably a lot of people and it shows, kudos in your direction.

Tarhoosier- good reply also, thanks for adding

Mel- Johns reply is what I have heard also for your questions

Our best appearing hope is at the cellular level to either repair the DNA that caused the normal cells to change to PCa, or effect the DNA in PCa by mechanisms like dendretic cell action, or some kind of genetic engineering concepts. This kind of stuff is being worked on right now and the market is axious for it. Logically this would be way better than all the drugs being used right now. Could become the break through.
Dx-2002 total urinary blockage, bPsa 46.6 12/12 biopsies all loaded 75-95% vol.; Gleasons scores 7,8,9's (2-sets), gland size 35 normal, ct and bone scans appearing clear- ADT3 5 months prior to radiations neutron/photon 2-machines, cont'd. ADT3, quit after 2 yrs. switched to DES 1-mg, off for 1 yr., controlled so well, resumed, using intermittently, pleased with results

Fairwind
Veteran Member


Date Joined Jul 2010
Total Posts : 3892
   Posted 8/20/2010 8:17 PM (GMT -6)   
I have a feeling they didn't take DES off the market because it worked so well.. Before anyone jumps on this bandwagon, they need to check out the entire load in the wagon...
Age today: 68. Married, 6', 215 pounds, active, no health issues.
PSA at age 55: 3.5, DRE negative. Advice, "Keep an eye on it".
PSA at age 58: 4.5
PSA at age 61: 5.2
PSA at age 64: 7.5, DRE "Abnormal"
PSA at age 65: 8.5, DRE " normal", biopsy, 12 core, negative...
PSA at age 66 9.0 DRE "normal", BPH, Finesteride. (Proscar)
PSA at age 67 4.5 DRE "normal" second biopsy, negative.
PSA at age 67.5 5.6, DRE "normal" U-doc worried..
PSA at age 68, 7.0, third 12 core biopsy positive for cancer in 4 cores, 3 cores Gleason 6, one core Gleason 9. Finesteride discontinued, still no urinary symptoms, never had any..From age 55 to 65 I had no health insurance.

I have a date with the robo surgeon on Sept 3 but I'm keeping my options open. I'm also looking at seeds combined with IGRT which seems to be having good results with high-risk patients..

Purgatory
Elite Member


Date Joined Oct 2008
Total Posts : 25393
   Posted 8/20/2010 8:56 PM (GMT -6)   
This is right from the CDC own web site on DES:

http://www.cdc.gov/des/hcp/nurses/history.html
Age: 58, 56 dx, PSA: 7/07 5.8, 10/08 16.3
3rd Biopsy: 9/08 7 of 7 Positive, 40-90%, Gleason 4+3
open RP: 11/08, on catheters for 101 days
Path Rpt: Gleason 3+4, pT2c, 42g, 20% cancer, 1 pos marg
Incont & ED: None
Post Surgery PSA: 2/09 .05,5/09 .1, 6/09 .11. 8/09 .16
Post SRT PSA: 1/10 .12, 4/8 .04, 8/6 .06 11/10 ?
Latest: 6 Corr Surgeries to Bladder Neck, SP Catheter since 10/1/9, SRT 39 Sess/72 gy ended 11/09, on Catheter #21, will be having Ileal Conduit Surgery in Sept.

Fairwind
Veteran Member


Date Joined Jul 2010
Total Posts : 3892
   Posted 8/20/2010 10:36 PM (GMT -6)   
DES was the "Gold Standard" of prostate HT 30 years ago.. Instead of dying from cancer, men died of a heart attack..

Dr. Walsh covers it on pages 452 and 453....
Age today: 68. Married, 6', 215 pounds, active, no health issues.
PSA at age 55: 3.5, DRE negative. Advice, "Keep an eye on it".
PSA at age 58: 4.5
PSA at age 61: 5.2
PSA at age 64: 7.5, DRE "Abnormal"
PSA at age 65: 8.5, DRE " normal", biopsy, 12 core, negative...
PSA at age 66 9.0 DRE "normal", BPH, Finesteride. (Proscar)
PSA at age 67 4.5 DRE "normal" second biopsy, negative.
PSA at age 67.5 5.6, DRE "normal" U-doc worried..
PSA at age 68, 7.0, third 12 core biopsy positive for cancer in 4 cores, 3 cores Gleason 6, one core Gleason 9. Finesteride discontinued, still no urinary symptoms, never had any..From age 55 to 65 I had no health insurance.

I have a date with the robo surgeon on Sept 3 but I'm keeping my options open. I'm also looking at seeds combined with IGRT which seems to be having good results with high-risk patients..

tarhoosier
Regular Member


Date Joined Mar 2010
Total Posts : 495
   Posted 8/21/2010 9:29 AM (GMT -6)   
Another way to present this is to know that at diagnosis every man has some PCa cells that have the POTENTIAL to divide in a low testosterone environment. Maybe that function exists or maybe the dna has mutated such that this function will arise in the future, while in other cells it will not. There is a term "genetic drift" which implies that some cells are without the function currently but in the future will develop this nasty feature. Some say that low testosterone environment causes this function, others say it reveals this function, while others say it allows it to develop at a later time.
Gleason score is relevant here also. Higher G means it is more likely that dna changes have created this adaptation. Men with G 3 and 2 can go on hormone therapy for long periods, decades, without this adaptation appearing.

zufus
Veteran Member


Date Joined Dec 2008
Total Posts : 3149
   Posted 8/21/2010 4:42 PM (GMT -6)   
If you read the Journal Article I posted above closely (sounds like some didn't even look at it), did you see the conclusion those doctors came too on using this??? This is in the Journal of Urology (Urologists bible publication in effect), for them to analyze this and come up with those findings....astounding for it to be published and put forth as those docs whom did all this research and collaboration to write this, also was not biased by a drug company or like a clinical trials abstract thing...quite interesting.

No nothing is perfection in PCa selections, having real choices and deciding for yourself could be important. Dr. Lee no doubt knows more about PCa than probably anybody on this forum...why did he use emcyt (an estrogenic)..didn't he know it would kill him???
He has been on it for a very long time with fab results, 27 yrs. with PCa in total. Dr. Lee Dx 1983 and is now 80 yrs. old still practicing medicine too. So, he made a mistake is what you are saying. If so I hope I can make the same mistake.
Dx-2002 total urinary blockage, bPsa 46.6 12/12 biopsies all loaded 75-95% vol.; Gleasons scores 7,8,9's (2-sets), gland size 35 normal, ct and bone scans appearing clear- ADT3 5 months prior to radiations neutron/photon 2-machines, cont'd. ADT3, quit after 2 yrs. switched to DES 1-mg, off for 1 yr., controlled so well, resumed, using intermittently, pleased with results

Post Edited (zufus) : 8/22/2010 9:48:23 AM (GMT-6)


el perro
Regular Member


Date Joined Mar 2010
Total Posts : 46
   Posted 8/22/2010 12:57 PM (GMT -6)   
Just wondering why folks go with DES vs. estrogen (or estradiol?) transdermal patches? I've read that some side effects might be lessened with the patch. Do they both do the same thing? I'm not trying to argue for/against DES, just trying to understand if there's an advantage to using DES in this situation?
Dx 11/2008, Gleason 3+3
Active surveillance for now

zufus
Veteran Member


Date Joined Dec 2008
Total Posts : 3149
   Posted 8/22/2010 1:53 PM (GMT -6)   
Don't forget to mention emcyt another estrogenic in this, worked fabulously in Dr. Lee at year 27 with PCa now. It might be superior, I don't know...it seems to have more possible side effects, as a trade off. All three of these estrogenics work some what similarly, but not totally identically looking very deep into them in all ways. Even some of the side effects very alittle between them.  Could say plenty more...but changed my mind.
 
Read this story psa 3000  (Dr. Sartor used DES) Trueman Seamans-1999 Dx
www.yananow.net/Mentors/TruemanS.htm    (I couldn't access it today, maintenance?)
 
I have to read it again on the site, this is from my notes I wrote down, I presume my info was on the money.
 
Dx-2002 total urinary blockage, bPsa 46.6 12/12 biopsies all loaded 75-95% vol.; Gleasons scores 7,8,9's (2-sets), gland size 35 normal, ct and bone scans appearing clear- ADT3 5 months prior to radiations neutron/photon 2-machines, cont'd. ADT3, quit after 2 yrs. switched to DES 1-mg, off for 1 yr., controlled so well, resumed, using intermittently, pleased with results

Post Edited (zufus) : 8/22/2010 3:44:39 PM (GMT-6)

New Topic Post Reply Printable Version
Forum Information
Currently it is Friday, September 21, 2018 8:30 AM (GMT -6)
There are a total of 3,005,381 posts in 329,221 threads.
View Active Threads


Who's Online
This forum has 161775 registered members. Please welcome our newest member, Thurman Kunde.
296 Guest(s), 10 Registered Member(s) are currently online.  Details
bluebird123, PeterDisAbelard., oceanfisher58, island time, cashlessclay, Missouri, BBN!!, UCer23, Everton, straydog