It appears you have not yet Signed Up with our community. To Sign Up for free, please click here....



Cancer: Prostate Message Board
Post New Thread   Closed Thread
LinkBack Thread Tools
Old 04-16-2011, 04:31 PM   #1
Senior Veteran
(male)
 
Join Date: Nov 2007
Location: Annandale, VA, USA
Posts: 1,730
Blog Entries: 3
IADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB User
Thumbs up Failed chemo, but superior survival

Prostate cancer patients for whom chemotherapy no longer controls the cancer have traditionally had a fairly short survival, with about 50% dead in twelve months, and most not surviving for two years.

A leading medical oncologist who specializes in prostate cancer talked to a support group near me today and described an approach he has been using since 2005 that has resulted in much better survival for such patients.

The approach has two key tactics: great attention to detail in caring for the overall health of the patient, and a three drug cocktail to go after the cancer.

Caring for overall health in these patients is key, because only a minority of deaths in this group are from prostate cancer - 39%; 33% of deaths involve cardiovascular issues, and 12% are due to colon cancer. Combined these three causes account for 84% of deaths in patients failing chemotherapy. He emphasized that flu kills more men than prostate cancer each year and is also one of the major reasons that men end up in nursing homes. Flu also causes strokes and heart attacks. Therefore, getting flu shots and taking steps to avoid flu helps cut the death rate in patients who have failed chemo as well as in other prostate cancer patients. Similarly, properly managing cholesterol and triglycerides and blood pressure is important, as is having men keep up their colonoscopies to provide prevention, early detection and cure of colon cancer. Shingles vaccination is important to prevent shingles from lowering the patient's overall health. These are some of the main examples of this approach.

The three drug combo uses transdermal estrogen, the least toxic form of hormonal therapy, as the first drug. The second drug is ketoconazole, about which researchers have learned a lot in the past decade, particularly includng Dr. Eric Small's classic work at UCSF. Alone, about 35% to 40% of prostate cancer patients respond to ketoconazole. (It's used with hydrocortisone to prevent a serious side effect, and the doctor noted that ketoconazole must be managed carefully because of substantial interactions with many other drugs and taken diligently every eight hours with an acid beverage - or something to make the stomach acid; Tylenol should not be taken by a patient on ketoconazole to avoid serious liver damage.) However, when the third drug, Leukine, is added, the combined response to ketoconazole and Leukine jumps to about 75% - about double! We also learned a key insight into the role of the New Investigational Drug Abiraterone, considered an almost sure bet for approval by the FDA for prostate cancer this year. Abiraterone functions similarly to ketoconazole, but it is considerably weaker; on the other hand, it will be sufficient for many patients, and it is much easier to manage than ketoconazole.

The doctor has had more than a hundred patients on this combined program starting in 2005 with remarkable success. About 80% have enjoyed very substantial plunges in their PSAs, with an impressive 29% achieving an undetectable PSA! The median (average) survival has been 40 months, and that will increase as there have been no deaths for five years!

The doctor noted that PSA responses to the regimen are usually fast - within eight weeks. If the patient turns out to be one of those who does not respond, then he is rapidly shifted to another approach.

Many of the details of the approach are discussed in the book "Beating Prostate Cancer: Hormonal Therapy & Diet."

I am in awe of these results, inspired by them and greatly encouraged by them.

Take care,

Jim

 
The Following User Says Thank You to IADT3since2000 For This Useful Post:
Baptista (04-18-2011)
Sponsors Lightbulb
   
Old 04-16-2011, 07:12 PM   #2
Inactive
(male)
 
Join Date: Aug 2010
Posts: 689
Tall Allen HB UserTall Allen HB UserTall Allen HB UserTall Allen HB UserTall Allen HB UserTall Allen HB UserTall Allen HB UserTall Allen HB UserTall Allen HB UserTall Allen HB UserTall Allen HB User
Re: Failed chemo, but superior survival

I would be cautious about estrogen therapy. I know it has a testosterone-suppressing effect, that it downgrades the androgen receptor, and that it activates an antiproliferative estrogen receptor in prostate cancer cells, ERβ. But it also seems to stimulate a pro-proliferative estrogen receptor, ERα, and also seems to stimulate PC stem cells. Also, it is quite toxic in men -- cardiovascular, breast tissue, and it severly impacts mood.

In the following study, they looked at testosterone, Sex Hormone Binding Globulin (SHBG), and Estradiol (the primary human estrogen) in men about to undergo prostatectomy. What they found will surprise many who think high testosterone contributes to prostate cancer.

There was no association between testosterone or SHBG and the incidence of high grade PC (Gleason≥4+3). High estrogen, however, was associated with more aggressive disease. Here's an abstract of the study:
http://www.ncbi.nlm.nih.gov/pubmed/21495024

The Morgentaler hypothesis, which has so far been borne out, is that only very small amounts of testosterone are needed to maximally stimulate the Androgen Receptor of PC cells. This is why there is no association between testosterone and high grade disease. I suppose adding abiraterone to the arsenal of triple blockade will help get T to a non-stimulating level.

Estrogen seems to be a two-edged sword. I suppose it must help more than it harms, or no one would use it. Hopefully, we'll have better alternatives soon (e.g., a selective ERβ stimulator).

- Allen

 
Old 04-16-2011, 08:34 PM   #3
Senior Veteran
(male)
 
Join Date: Nov 2007
Location: Annandale, VA, USA
Posts: 1,730
Blog Entries: 3
IADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB User
Re: Failed chemo, but superior survival

Hi Allen,

I just want to clarify an important point about using estrogen for prostate cancer treatment. I'll try to get to other points you raised in the future. You wrote in part in the immediately preceding post:


Quote:
Originally Posted by Tall Allen View Post
I would be cautious about estrogen therapy. I know it has a testosterone-suppressing effect, that it downgrades the androgen receptor, and that it activates an antiproliferative estrogen receptor in prostate cancer cells, ERβ. But it also seems to stimulate a pro-proliferative estrogen receptor, ERα, and also seems to stimulate PC stem cells. Also, it is quite toxic in men -- cardiovascular, breast tissue, and it severly impacts mood.

...
Estrogen seems to be a two-edged sword. I suppose it must help more than it harms, or no one would use it. Hopefully, we'll have better alternatives soon (e.g., a selective ERβ stimulator).

- Allen
The critical point is that transdermeral estrogen, which is delivered through patches on the skin, is safe, in contrast to the older kind of estrogen delivery that has proven to have the risks you mentioned, and it is quite effective. It will grow breast tissue, but that can be countered. I have not heard about any problems with mood for men on transdermal estrogen; I suspect that is not an issue, but I don't know for sure.

The doctors I consider leaders are enthusiastic about it and use it extensively in second line hormonal therapy. As they have large practices and have used it for a number of years now, there is some substantial evidence that it is a worthwhile approach.

Take care,

Jim

 
Old 04-16-2011, 11:03 PM   #4
Inactive
(male)
 
Join Date: Aug 2010
Posts: 689
Tall Allen HB UserTall Allen HB UserTall Allen HB UserTall Allen HB UserTall Allen HB UserTall Allen HB UserTall Allen HB UserTall Allen HB UserTall Allen HB UserTall Allen HB UserTall Allen HB User
Re: Failed chemo, but superior survival

Transdermal patches have the advantage of steady, even delivery, which eliminates the more toxic peaks one gets with injections. I agree that it's an advantage over injections, but the problem remains that estrogen has both anti- and pro-proliferative effects. I doubt there's any way around it with estrogen.

 
Old 04-17-2011, 04:40 AM   #5
Senior Veteran
(male)
 
Join Date: Nov 2007
Location: Annandale, VA, USA
Posts: 1,730
Blog Entries: 3
IADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB User
Re: Failed chemo, but superior survival

Hi Allen,

I'm responding to your immediately preceding post.

There is another big advantage of transdermal estrogen. The old estrogen DES (diethylstilbestrol) was taken by mouth, and it was very effective in reducing testosterone and "kill[ing] prostate cancer cells by binding to estrogen receptor beta in these canceer cells. Thus estrogenic drugs can be very effective in men who no longer respond to testosterone blockage." (from Beating Prostate Cancer: Hormonal Therapy & Diet," original edition, page 97, Dr. Charles "Snuffy" Myers") However, use of this drug dropped sharply when a clinical trial showed that "oral estrogens caused severe cardiovascular side effects that killed almost as many men as they saved...." (same source)

The key advantage of the transdermal estrogen is that it is not taken by mouth and therefore does not go through the liver, which reduces clotting factors and thereby blood clots. "Beating" has a table on page 98 showing that transdermal estrogen causes no increase in angiotensin precursor, in C-reactive protein, causes no suppression of IGF1, and causes no increase in clotting proteins and pulmonary embolism, all problems with oral estrogen. (However, with modern drugs to counter side effects, even DES, which is cheap, can be safely managed with some effort.) The transdermal form has been widely studied in women.

"Beating" also notes that transdermal estrogen "is much less expensive than any other form of hormonal therapy."

I would say the bottom line of transdermal estrogen for advanced prostate cancer is that it has proven to work well in actual medical practice. Check it out.

Take care,

Jim

Last edited by IADT3since2000; 04-17-2011 at 04:43 AM. Reason: added phrase "to counter side effects" for DES

 
Old 04-17-2011, 10:56 AM   #6
Inactive
(male)
 
Join Date: Aug 2010
Posts: 689
Tall Allen HB UserTall Allen HB UserTall Allen HB UserTall Allen HB UserTall Allen HB UserTall Allen HB UserTall Allen HB UserTall Allen HB UserTall Allen HB UserTall Allen HB UserTall Allen HB User
Re: Failed chemo, but superior survival

One can avoid first-pass metabolism by the liver and many of the ensuing liver problems with transdermals -- no question.

The BIG problem, and I don't know whether Dr. Myers addresses this or not, is that estrogen stimulates prostate cancer by activating the estrogen alpha receptor.

On pubmed, I entered "ERalpha AND "prostate cancer" in the search bar and came up with 317 research articles on the subject. Most of these are about how it stimulates prostate cells to become cancerous, how it stimulates prostate cancer cells to become more invasive, and how it stimulates prostate cancer stem cells.

Fortunately, scientists are studying ways to activate only the beta receptor without activating the alpha receptor. They are investigating whether more selective estrogens and selective estrogen receptor modulators (SERMs) might do this.

Even more exciting to me is the area of Selective Androgen Receptor Modulators (SARMs). Drug companies have developed SARMs that are tissue-specific to the prostate. That is, they will shut down the Androgen Receptor (AR) in prostatic tissue without shutting it down in the muscle, bones or brain. Conversely, there are SARMs that only activate the AR in non-prostatic tissues. All of these are in very early phases of testing and development.

- Allen

 
The Following User Says Thank You to Tall Allen For This Useful Post:
Baptista (04-18-2011)
Old 04-21-2011, 01:45 PM   #7
Senior Veteran
(male)
 
Join Date: Nov 2007
Location: Annandale, VA, USA
Posts: 1,730
Blog Entries: 3
IADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB User
Re: Failed chemo, but superior survival


ESTROGEN RECEPTORS ALPHA AND BETA FOR PROSTATE CANCER - LAB, ANIMAL AND HUMAN RESEARCH IN PERSPECTIVE

Hi Allen,

I'll insert some thoughts in green in an excerpt of your just previous post about how I look at such scientific evidence. I've been exposed to a lot of it when I go to medical research conferences as a survivor representative, and it's important to find a way to separate the wheat from the chaff, so to speak. That said, thanks for focusing our attention on estrogen receptor alpha. It's worth keeping an eye on that.


Quote:
Originally Posted by Tall Allen View Post
...

The BIG problem, and I don't know whether Dr. Myers addresses this or not, is that estrogen stimulates prostate cancer by activating the estrogen alpha receptor.
I am highly confident that he is aware of it, though he has not mentioned it in his talks. That would be consistent in his approach of helping patients understand what they need to know from a practical, operational standpoint, helping them know what they should do without burdening them with points that do not bear directly on benefits to them and their decision making, however interesting those points may be to scientists and potentially important to drug developers.

Quote:
On pubmed, I entered "ERalpha AND "prostate cancer" in the search bar and came up with 317 research articles on the subject. Most of these are about how it stimulates prostate cells to become cancerous, how it stimulates prostate cancer cells to become more invasive, and how it stimulates prostate cancer stem cells.
I took a quick look at some of the abstracts, and I see the concern. However, I'm confident that what is happening is this:
- estrogen has both (at least) estrogen receptors (ER) alpha and beta, the docking ports for getting estrogen into the cells;
- ER alpha apparently, on balance, promotes prostate cancer;
- ER beta works against prostate cancer;
- on balance, ER beta is far more dominant than ER alpha, meaning that there is a great net benefit from taking estrogen in a form that will avoid side effects. That great net benefit has been abundantly demonstrated in medical research.

This kind of thing often happens to the medications and nutrients we take. In lab (cells in culture, for example, such as Petri dish research) and animal studies, medications and nutrients often demonstrate potentially useful or harmful effects. However, in the actual, living human body environment, those effects are often not there - they have been neutralized, or sometimes even reversed. That's why it is so key to focus on studies in humans. Paying some attention to lab and experimental studies is informative as background, but the acid test is human studies. That is a key viewpoint that helps me sort through the ton of research being produced every year.

Here is a way to access some of the medical research in actual human patients on estrogen for protstate cancer. I just searched www.pubmed.gov for " prostate cancer AND estrogen ", which yielded 318 hits, with 41 providing links to free full text articles. However, that list includes many in which estrogen and prostate cancer are incidental mentions. I narrowed the list by activating the Limits feature with these limits: only items with abstracts, Humans, Male, Clinical Trial, Field: MeSH Major Topic. The Field limit gets rid of many incidental mentions. This reduced the list to 37 hits, including ten with free links to full text articles. I scanned a few of the abstracts, and this looks like a motherload of what we want - estrogen as it works in actual human prostate cancer patients. I also saw the powerful results that I was expecting.


Quote:
Fortunately, scientists are studying ways to activate only the beta receptor without activating the alpha receptor. They are investigating whether more selective estrogens and selective estrogen receptor modulators (SERMs) might do this.

Even more exciting to me is the area of Selective Androgen Receptor Modulators (SARMs). Drug companies have developed SARMs that are tissue-specific to the prostate. That is, they will shut down the Androgen Receptor (AR) in prostatic tissue without shutting it down in the muscle, bones or brain. Conversely, there are SARMs that only activate the AR in non-prostatic tissues. All of these are in very early phases of testing and development.

- Allen
I'm thinking that estrogen, modified as you are describing, would be even more powerful as a therapeutic agent for prostate cancer. That's something to hope for, but for now, the transdermal estrogen patches are powerful therapy that is already available.

Take care,

Jim

 
Old 04-21-2011, 02:14 PM   #8
Senior Veteran
(male)
 
Join Date: Nov 2007
Location: Annandale, VA, USA
Posts: 1,730
Blog Entries: 3
IADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB User
Cool Re: Failed chemo, but superior survival

RADIATION FOR PROSTATE CANCER PATIENTS FAILING CHEMOTHERAPY?

That seems like an illogical approach. You would think that such patients would have already benefited as fully from radiation as possible. Yet, that is not always the case.

For a minority of these patients, but a substantial minority of 20% seen in one leading practice that treats many advanced cases, the metastasized cancer is in just a few spots. In research terms that is known as "oligometastatic" cancer ("oligo" meaning "few"). What is so encouraging is that these patients can now get a second shot at a cure by targeting these spots with precisely targeted cancer-killing radiation!

The trick is to isolate the spots, and this was not possible until the development of the Combidex/Sinerem scan, practiced until recently in the Netherlands. (Of course, it's wonderful that we now have radiation imaging and delivery systems that can precisely deliver the needed doses.) That scan, generically known as a high-resolution MRI scan with an Ultrasmall Superparamagnetic Iron Oxide (USPIO) contrast agent, was highly sensitive and highly specific for picking up cancer in lymph nodes. A very similar and apparently equally effective scan is now available in Orlando, in the US, and resercher physicians are laying the foundation for widespread availability of the scan. The US scan involves a contrast agent known as feraheme (from words for iron and blood). It is outstanding at precisely locating the cancer - displaying the actual lymph node affected - as well as identifying it! Amazing stuff!

One of the experts researching use of the scan said that the scan is not useful until the PSA hits 2.0. It can pick up tumors as small as an eighth of an inch - just a few millimeters. The expert said he thought it would supplant the ProstaScint scan.

What a wonderful development for late-stage patients!

Jim

 
Old 04-21-2011, 03:23 PM   #9
Senior Veteran
(male)
 
Join Date: Nov 2007
Location: Annandale, VA, USA
Posts: 1,730
Blog Entries: 3
IADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB UserIADT3since2000 HB User
Re: Failed chemo, but superior survival

USING GENE ANALYSIS TO FIND EFFECTIVE DRUGS FOR ADVANCED CASES

A leading expert in helping prostate cancer patients with late stage disease included a brief but very interesting point in a talk this past Saturday: using genetic analysis, now - not in the future, to pinpoint which unusual drugs were likely to work for specific patients based on analysis of their genes. For instance, based on a patient's genes, it might turn out that his prostate cancer would be susceptible to drugs normally used for, let's say as an example, lung cancer! This means that "cocktails" of drugs (combinations) can be identified that are likely to help the patient, and that drugs which look unpromising for a particular patient can be avoided. One specific success he mentioned was using Abraxane, a drug for metastatic breast cancer that combines proven chemotherapy, paclitaxel, with albumin, for a prostate cancer patient, based on genetic analysis!

I've been hearing about the advent of such highly personalized genetically based medical decision making for several years at the cancer research conferences I have attended as a survivor representative. However, this is the first time that I've heard of a doctor primarily in clinical practice for prostate cancer and not research is using this technology to help his patients. He said that he has had some dramatic favorable responses with this approach.

The HER genes have been used for years now to decide whether chemotherapy would be helpful for breast cancer patients. However, the doctor's use of genetic analysis is a bit different. Rather than checking for a major gene such as HER, the patient's cancer gets a broad spectrum gene check, as I understand it, and vulnerabilities are identified. The doctor mentioned that the technology is located in Texas, and I thought he mentioned the name Karras. I haven't been able to pin down the facility, but I think it might be the "AT&T Genomic Computing Center" at the "Texas Biomedical Research Institute." The facility has an enormous computational capability, and they state that "analyses that once took months now take minutes." It uses its capability to find genes that influence disease.

Once again, I'm awed by the wonder of the advances being made that may well benefit those of us with advanced cases.

Jim

 
The Following User Says Thank You to IADT3since2000 For This Useful Post:
Baptista (04-21-2011)
Closed Thread

Similar Threads
Thread Thread Starter Board Replies Last Post
Failed Prostatectomy :( honda50 Cancer: Prostate 32 03-10-2011 11:38 AM
Chemo Phase 2 Trial at NCI DonD Cancer: Prostate 2 03-09-2011 03:01 AM
Projection of 15-year Prostate cancer Specific survival Baptista Cancer: Prostate 11 02-02-2011 09:33 AM
PSA 4.4, what is survival rate with no treatment? Bryan73 Cancer: Prostate 4 05-09-2010 01:44 PM
chemo and recurring prostate cancer: not the best option at this time ? flyfisher37 Cancer: Prostate 10 01-07-2009 10:46 AM

Tags
chemo, ketoconazole, leukine, survival, transdermal estrogen



Thread Tools

Posting Rules
You may not post new threads
You may not post replies
You may not post attachments
You may not edit your posts

BB code is On
Smilies are On
[IMG] code is Off
HTML code is Off
Trackbacks are Off
Pingbacks are Off
Refbacks are Off




Join Our Newsletter

Stay healthy through tips curated by our health experts.

Whoops,

There was a problem adding your email Try again

Thank You

Your email has been added




Top 10 Drugs Discussed on this Board.
(Go to DrugTalk.com for complete list)
Casodex
Cialis
Cipro
Flomax
Levaquin
  Levitra
Morphine
Proscar
Tylenol
Viagra




TOP THANKED CONTRIBUTORS



Tall Allen (174), IADT3since2000 (148), Baptista (97), Gleason9 (28), harpman (27), Johnt1 (22), honda50 (9), tumbleweed (6), flyfisher37 (6), bharlan (5)

Site Wide Totals

teteri66 (1165), MSJayhawk (1000), Apollo123 (898), Titchou (833), janewhite1 (823), Gabriel (758), ladybud (747), sammy64 (668), midwest1 (665), BlueSkies14 (610)



All times are GMT -7. The time now is 03:51 AM.



Site owned and operated by HealthBoards.comô
Terms of Use © 1998-2014 HealthBoards.comô All rights reserved.
Do not copy or redistribute in any form!