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Intermittent Hormone Therapy Fails the Test

hopeful and opt...
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Intermittent Hormone Therapy Fails the Test
Posted: 03 Jun 2012 03:58 PM PDT
A very important randomized study is being presented at the ASCO meeting and appears to show that intermittent hormone therapy results in a worse survival in men with metastatic prostate cancer compared to men on continuous therapy. This is consistent with another study done in Europe and it is important for many reasons, most importantly it is another example of the need to do a randomized study to properly evaluate if a treatment is good enough. A full video will be done next week. (June 4, 2012)

I will post follow up info next week. This is from Prostate Videos.com, Dr.Chodak

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VascodaGama
Posts: 1531
Joined: Nov 2010

Hopeful

Thanks for the interest on this treatment and all the comments you may render. Intermittent HT is very important to my case.
Nevertheless, Dr. Chodak has shown before some negativeness through wards the treatment modality when the Canadian study was presented and “absorbed” by ASCO members.
The Uro associations norms take still “intermittent” as experimental.

I am hopeful for your next post and the video.

Regards
VG

hopeful and opt...
Posts: 1293
Joined: Apr 2009

http://www.webmd.com/prostate-cancer/news/20120604/stopping-hormone-therapy-shortens-mens-lives?src=RSS_PUBLIC
Prostate Cancer Patients on Continuous Hormone Therapy Lived Longer Than Patients Given Intermittent Treatment, Study Finds
By Charlene Laino
WebMD Health News
Reviewed by Laura J. Martin, MD

June 4, 2012 (Chicago) -- Taking a break from hormone therapy can shorten the lives of some men with metastatic prostate cancer, researchers say.
Many men take a break from hormone therapy -- aka androgen-deprivation therapy or ADT -- to lessen its often debilitating side effects.
ADT -- which turns off production of the male hormone testosterone that fuels the growth of prostate tumors -- is a first line of treatment for metastatic disease (that has spread beyond the prostate).
But because hormone therapy blocks male hormones, it can lead to loss of sexual function and severe hot flashes. Over time, weakened bones (osteoporosis) andheart problems may develop.
But in a new study of more than 1,500 men tracked for nearly a decade, patients with minimal cancer spread given continuous ADT lived an average of about two years longer than those given intermittent (on-again, off-again) ADT.
Interrupted ADT should no longer be recommended as an initial treatment, says researcher Maha Hussain, MD, of the University of Michigan Comprehensive Cancer Center in Ann Arbor, Mich.
"Continuous therapy continues to be the standard of care," she tells WebMD.
Hussain reported the findings here at the annual meeting of the American Society of Clinical Oncology.
Slideshow: A Visual Guide to Prostate Cancer
Intermittent ADT
Prostate cancer is the second most common cancer in men, with nearly 242,000 cases diagnosed each year in the U.S., according to the American Cancer Society.Skin cancer is the most common.
Previous smaller studies suggested that intermittent hormonal therapy -- stopping and restarting treatment periodically -- was as effective as continuous therapy, but with a lower risk of these side effects, says Bruce Roth, MD, a prostate cancer specialist at Washington University School of Medicine in St. Louis. Roth, who was not part of the study, moderated a news briefing at which the findings were presented.
As a result, interrupted ADT became widely used in the U.S., he tells WebMD.
"But this study for the first time indicates that there is a price to pay. Men need to ask themselves if they are willing to trade hot flashes for two years of their lives," he says.
Continuous ADT Beats Out Intermittent ADT

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VascodaGama
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Joined: Nov 2010

Hopeful

I am speechless for the news. It worries me that controversy on HT modalities has begun at ASCO levels.
The study was funded by the U.S. National Cancer Institute and AstraZeneca Pharmaceuticals which is the owner of Zoladex. A study recommending lesser use of drugs may not be what they would want as a conclusion. Am I cynical or logically thinking?

In any case the study is real and their conclusion outstanding. This contrasts with previous studies (phase III) submitted also to ASCO, where the conclusion was that;

“… IHT have a beneficial effect on the incidence of side-effects, on QoL, and on cost. Additionally, IHT have no negative impact on overall survival or progression-free survival compared to continuous hormone therapy”.

Surely this is not what I wanted to read now when I just started the Off-drugs vacation on mine hormonal treatment.

My opinion is that both modalities are good depending on the patient status and surely on other aspects like; the protocol, length of the cycles (on and off) and parameters (trigger thresholds marks). Dr. Myers is known to recommend starting the off cycle when a patient has been in “remission” (PSA<=0.01) for at least one year. Others prefer the threshold of PSA <=0.05 (my doctor).

Hopefully better understanding in HT protocols is developed to the benefit of the many.

Thanks for the post.

VG

Samsungtech1
Posts: 350
Joined: Jan 2011

Vasco,
Things have changed so fast in the last couple of years that I am a little cautious about studies done by the maker of the drug. In my line of work I call it the Million dollar lunch. You take a reviewer out to lunch, give him money, and your product is the greatest thing since sliced bread.
I believe everyone of us are doing what we think is best to prolong our survival. When you look at the actual increases in longevity it only looks good if you are on the surviving percentage. My side effects were so bad that I quit a month after my second injection. My choice. We all have to make decisions like this all the time. I felt the cure was not worth the side effects I was going through.
As far as you and your doctor; well you have to trust someone. He sounds good to me. I would look into percentages on this. See exactly how it breaks down. If it is a 30-40 per cent difference then It would be worth considering. Most are 10-17 per cent. When you figure the screening process that probably is worth two to three per cent bias. Check it out.

You are smarter at the research than I will ever be. I do it on an as needed basis. When it happens I look into it.

Mike

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Kongo
Posts: 1167
Joined: Mar 2010

This is an interesting study. My previous readings had led me to believe there was little difference in long term outcome between continual and intermittent HT although to me it always seemed counter intuitive that this would be.

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VascodaGama
Posts: 1531
Joined: Nov 2010

Mike

Thanks for the comments. I received yesterday “alarming” calls from friend doctors (Portugal, US and Japan) who know about my protocol. The news is moving fast around the world and worrying many guys.

Interesting is that your comment is relevant (percentages) and the study’s basic details indicate just that “the conclusion is for a certain cohort of patients only”, which pertain to SWOG trial (Southwest Oncology Group).
Nevertheless, the percentage varies without any established pattern. More else, these are results from specific patients diagnosed with:
1) Stage IV D2 prostate cancer (extensive severity group) at bones and organs; and
2) Stage N0, high PSA (above 5 ng/ml to 48,000 ng/ml) or positive PAP (minimal severity group).

However, patients with a Gleason score above 7 (high risk) comprised the majority of the participants (52%). Lower Gs below 7 were only 17%.

Another important aspect is that only 20% of the total numbers were guys with previous prostatectomy. Patients with previous or post radiotherapy and orchiectomy were not included in the study but previous chemotherapy was accepted.

Data comes from this study;
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2684851/

The overall results were picked from guys that were on continuous hormonal treatment (ADT2 of Zoladex plus Casodex) and for those that followed a regimen intermittently. In saying that, this group was uniformly composed of guys that stopped the medication (start of Off-drug period) after 8 months on-drugs and that managed to have a confirmed stable PSA of 4 ng/mL or less, with a declining trend.

Unfortunately the study does not include/integrate HT patients on single blockade (LHRH agonist) which is my case; neither it includes patients on triple blockade (LHRH agonist plus antiandrogen plus 5-ARI).

At conclusion, the researchers compared the Arm I (continuous HT therapy against Arm II (intermittent HT therapy): and found that the median overall survival time for those with minimal disease was 7.1 years on continuous compared to only 5.2 years on intermittent treatment. Patients with extensive disease had median overall survival times of 4.4 years on continuous therapy and 5.0 years on intermittent therapy.
In any case Dr. Maha Hussain, the researcher, ends with this comment;
“…Based on this study’s findings, it seems that one size does not necessarily fit all,”

http://www.uofmhealth.org/news/cancer-prostate-0604

As for the AstraZeneca Pharmaceuticals interests, one could see it both ways. as a “Million Dollar lunch” or as a “Punch in the Nose”.

If Continuous is in fact better and it is adopted by the medical associations and recommended in world practice guideline standards, then one could get Bilateral Orchiectomy (permanent castration) instead of buying Zoladex.
Intermittent is only possible in treatments were the chemical castration induced by LHRH agonists can be stopped.

The researcher was fair in her conclusion that intermittent gives better results in terms of Quality of Life, in both; Global quality of life (libido, physical, vitality and emotional) and Health quality of life (related incidental illnesses).

I hope that my comrades reading this thread do not opt for continuous HT treatment just based on the presentations. Each case is different and it should be analysed based on one’s diagnosis and status.

Again, thanks for the comments and to all that shared their opinions.

VGama

mrspjd
Posts: 688
Joined: Apr 2010

Charles (Chuck) Maack is a twenty year PCa survivor with recurrence and on IAD. He is well known nationally & respected in the PCa community as a knowledgeable layman advocate/activist for prostate cancer awareness & education.

Regarding the recent study indicating Continuous Androgen Deprivation provided longer survival than Intermittent Androgen Deprivation, I felt that Mr Maack's thoughtful & informed perspective on the issue was relevant to this discussion. Following are his comments:

"What isn't explained here is what were the medications prescribed as androgen deprivation therapy (ADT) during that initial 7 month period? And more interesting, that by 7 months their PSA had fallen to only 4.0ng/ml? With appropriate ADT a patient's PSA should have dropped down into the ultrasensitive/3rd generation PSA levels below 0.1ng/ml within three to four months.

Following the protocol of Medical Oncologist Stephen Strum, intermittent androgen deprivation therapy (IAD) should not begin until the patient's PSA has dropped to <0.05ng/ml and testosterone to near or below 20ng/dl, and then having maintained those low, clinically castrate levels, for at least 12 months. I believe Medical Oncologist Charles "Snuffy" Myers uses these same levels as guidelines, but is comfortable with patients moving to IAD after 9 continuous months maintaining those levels. And the medications prescribed for ADT by these physicians are an antiandrogen, an LHRH agonist (or GnRH antagonist), and a 5AR inhibitor - triple hormonal blockade. I doubt that the medications prescribed during the 7 month period in this study that led to a PSA drop of only 4.0ng/ml included these three different forms of ADT medications. And I further doubt that when returning to ADT medications when PSA levels increased for those in the intermittent phase of the study, that these three different forms of medication were prescribed."

"In other words, only reaching a down-trend of PSA to only 4.0ng/ml at 7 months would not even qualify for intermittent androgen deprivation. In my opinion, using the PSA level of 4.0ng/ml as the study baseline for IAD or continuous ADT flawed the study. A drop in PSA over a 7 month period to only 4.0ng/ml is an indication that the medications prescribed as the ADT were either insufficient or only sufficient to hopefully sustain that level with continuous ADT. Under normal circumstances, intermittent androgen deprivation would not even be considered."

"Interestingly, I, along with several other men of whom I am aware who would be among the "minimal spread," must be in the minority in this regard. Here I am nearly 16 years following beginning the ADT/IAD (androgen deprivation therapy followed by intermittent androgen deprivation on a repetitive cycle). I have no idea of the medications that were prescribed to the men in the study but in my case and in the case of others of whom I am aware, our practice has been triple hormonal/androgen blockade that included an antiandrogen, an LHRH agonist, and a 5Alpha Reductase (5AR) inhibitor, and here we are many years (well beyond the 5 and 7 years identified) still looking down at the grass rather than up at the roots. Our off times permitted a return of testosterone and improvement in many quality of life issues. Not commented in this study of "continuous" androgen deprivation therapy vs IAD is that men on continuous shut down of testosterone production over 2 1/2 to 3 years are likely never going to recover reasonable testosterone levels, since their system goes into ‘andropause.’ One thing of particular note is the comment by Dr. Lepor regarding noting the likelihood of continuous fatigue, continued loss of libido, continued muscle loss in the absence of testosterone as part of continuous ADT."

"From my experience and the experiences I am aware of others, I will continue to promote not only triple hormonal/androgen blockade, but also intermittent androgen deprivation for those men whose PSA level drops to <0.05ngml and testosterone near or below 20ng/dl while on ADT medications and hold at those levels for at least 12 months. Then, when going off the antiandrogen and LHRH agonist, continue the 5AR inhibitor to continue to inhibit returning testosterone from converting to the more powerful stimulant to PC cell growth, dihydrotestosterone/DHT. Should PSA subsequently begin elevation, my recommendation is to not wait longer than a 2.0ng/ml level before returning to the antiandrogen followed by the LHRH agonist a week or so later (or at the same time if returning to the GnRH antagonist degarelix/Firmagon). Should PSA and testosterone levels again drop to clinically castrate levels and again remain at those levels for another 12 months, again repeat the IAD cycle."
###

Best to all,
mrs pjd

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VascodaGama
Posts: 1531
Joined: Nov 2010

In this video, fellow comrades can listen to the comment from Dr. Myers with regards to the presentation of the above controversy study submitted at ASCO meeting.

http://askdrmyers.wordpress.com/?mkt_tok=3RkMMJWWfF9wsRonuK7NZKXonjHpfsXx6OosT%2Frn28M3109ad%2BrmPBy%2B2YABWoEnZ9mMBAQZC81x0gNLDuGBeYZP6OBQ

According to Dr. Myers the media has given opinions on the study that are not true or represent a definite acceptable view of ASCO. He comments that the concept behind the results in the study may be questionable. Particularly when comparing the Continuous versus Intermittent modalities in a poorly managed control of the status of the patients.
The fact regulating the meaning of intermittent has been based on the time one was on the drugs (8 months) more than on the period under the status of castration (testosterone level). However, by experience, “…the majority of HT patients take 6 months to get to normal levels of testosterone…” circulating in the body.
In another words, the intermittent cohort has not been properly in a total off the effects of the drugs in the intermittent period before re-starting the on-drugs cycle.

In my view, such comment would mean that many of the patients in the intermittent cohort would actually fall within the group in continuous therefore their data should be included in the continuous results.

Again, I believe that intermittent is the way to choose but carefully and respecting the patterns of real status. Chemical or surgical castration can only be accessed through tests on T; and cycles on/off should be defined with levels of response by the cancer in PSA tests. The treatment then should be considered in failure when on castration a patient sees his PSA rise.

The best to all my friends.

VGama

Samsungtech1
Posts: 350
Joined: Jan 2011

Vasco,
I agree with you. My doctor just went to a meeting last week and said the word was continous. I asked him if he checked the tests to see how they were done. He said no. Said it was a series of presentations. Tolsd him to check the stats. He said he would.

Money vuys everything even though it can kill people. What a world.

Hope you are doing well.

Mi,e

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VascodaGama
Posts: 1531
Joined: Nov 2010

Contradictory Study

I think it proper to include in this thread the news about a recent published study (Aug/Sep 2012) that contradicts the main subject of this thread discussed above.
In this study the authors found that Intermittent Androgen Suppression (HT or ADT or any other name they call it) was non inferior to Continuous therapy with respect to overall survival.
What makes me to believe in its “excellency” is that the group of patients were tested for castration levels (drug’s effectiveness) and therefore improving recovery (normal range of T levels) while on Off drugs. The period of intermittent was not “fixed” as done in the study by Hussain, but dependent on rising PSA.
This is more convincing for a superior modality in the administration of HT not just for survival but for overall well being.

Here is the link;
http://www.ncbi.nlm.nih.gov/pubmed/22931259

VG

ob66
Posts: 215
Joined: Apr 2010

The logic of intermittent is just stronger, and not going to the ultralow levels on the PSA while under hormone therapy just seemed not right. The hormone must be detected as working, witness the O.05 or less readings, and must work for a period of time. Then, given too much time, the cancer cells can find ways around the hormone, thus the case for intermittent. I was on for two years after both daVinci and RadTherapy, and just got off. My readings were O.01 or less the entire time. Now, I need to sweat out the next reading in the late fall. Thanks for the update. If just sounds so much more logical, as well as more comforting.

fightn9er
Posts: 13
Joined: Aug 2012

Thank you all,

Gleason 9 PSA 26 CAT scan and Bone scan negitive, ECE and PIN both present.

Now it's decission time. 2nd opinions have been done. I have read and read. The info you guys posted here was reassuring.

KTF and the fight, I will.
Mike

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VascodaGama
Posts: 1531
Joined: Nov 2010

(Mike) Fightn9er

I like the way you move.
You have educated yourself in PCa treatments, you know about the risks and the side effects associated so now you are ready for a treatment. You need to consider a place where to get treated probably not too far from where you live so that you got assured “after care”. You should find a team of specialists in PCa (physicians) you trust. Your family should be behind any decision and you need to include aspects regarding your continuing professional life.

Your decision will be the best to handle your case. Trust it.

Hope for the best.
VGama

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