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Old 06-05-2012, 06:37 AM   #1
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Intermittent hormone therapy inferior to continuous therapy ?

A study on HT modalities (continuous VZ intermittent) done by Dr. Maha Hussain, of The University of Michigan Comprehensive Cancer Center, found that;

“…intermittent androgen-deprivation (AD) therapy is not as good as continuous hormone therapy with regard to patient longevity”.

The study, funded by the U.S. National Cancer Institute, was reported Sunday at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

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.

What should one believe in?

My opinion is that both modalities are good depending on each 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. The re-start of HT, however, depends on each case but some patients use a PSA=5 or =10, if on ADT3 or ADT2.

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

Baptista

 
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Old 06-05-2012, 09:13 AM   #2
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Re: Intermittent hormone therapy inferior to continuous therapy ?

Hi Baptista,

I agree it was a shocking and unexpected finding. And it was a well done study -- a 17 year study at more than 500 sites, enrolling 3,040 men with hormone-sensitive, metastatic prostate cancer between 1995 and 2008.

Men on continuous therapy had a median overall survival time of 5.8 years , with 29 percent of these men surviving at least 10 years. Those on intermittent therapy had a median overall survival time of 5.1 years, with 23 percent surviving at least 10 years, an 8 month advantage, which was statistically significant.

They found that the disavantage of intermittent therapy was even worse among those who had lesser amounts of metastatic disease to begin with. Such patients survived on the average for 5.2 years on intermittent therapy vs 7.1 years for continuous therapy, a 1.9 yr advantage for continuous.

On the other hand, those who began treatment when they already had more extensive disease survived 4.4 yrs on continuous vs 5.1 yrs on intermittent, an 8 month advantage for intermittent, which wasn't a statistically significant difference.

As you point out, they didn't include ADT3 in their study, so it's impossible to tell how much, if any, difference that might have made. However, all the men in the study had a very good response to their initial course of androgen deprivation. Perhaps more importantly, it doesn't include the ability of this new generation of hormone treatments like Zytiga (abiraterone) and the soon-to-be-approved enzalutamide (formerly, MDV 3100), and many others still in clinical trial, to extend the hormone-responsive phase.

I also agree with you that individual responses may vary. The variance in response between men who initially present with more aggressive vs less aggressive disease is an indicator of that. It becomes more important than ever to identify disease sub-types. For a small segment of men, intermittent may turn out to be at least as good as continuous.

I think that it forces us to consider how important quality of life is to us. If we have the opportunity to live out half our time in better mental, physical and sexual health, is that worth the cost of a few extra months? This is a very hard decision that many of us will have to struggle with. I don't think that intermittent therapy will disappear, although I think its use will be curtailed.

- Allen

 
Old 06-06-2012, 06:08 AM   #3
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Re: Intermittent hormone therapy inferior to continuous therapy ?

Allen

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.

In any case, the cohort of patients from whom the data were picked does not fit all cases.
Only stage IV D2 prostate cancer (extensive severity group) and N0, high PSA (above 5 ng/ml to 48,000 ng/ml) or PAP (minimal severity group), were considered.
These were also guys on ADT2 (not my case) and the majority were patients with a Gleason score above 7 (high risk) comprising 52% of the participants. Lower Gs below 7 were only 17%.

The AstraZeneca Pharmaceuticals (Zoladex) one of the funding sponsors may be furious at the results.
If Continuous is in fact better, adopted by the medical associations and recommended in world practice guideline standards, then one could get Bilateral Orchiectomy (permanent castration) instead of buying Zoladex or other LHRH agonist.
Intermittent is only possible (I believe) in treatments were the chemical castration induced by LHRH agonists can be stopped. No one would try it with constant TRT.

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).

Baptista

 
Old 06-06-2012, 03:28 PM   #4
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Re: Intermittent hormone therapy inferior to continuous therapy ?

CRUCIAL POINT MISSED BY MANY: STUDY DONE WITH METASTATIC MEN ONLY!!! FINDING FITS WITH LONG-TIME VIEWS OF EXPERT CLINICAL DOCTORS

Baptista - you can relax! (But from some misleading comments in the news I understand why your friends are concerned.)

Allen - We have probably both seen some of the same comments, but some of the commenters were misguided.

Here's the bottom line: For many years experts in ADT have generally recommended continuous ADT for prostate cancer patients who had metastatic disease, which fits with the findings in this study, while at the same time strongly recommending intermittent ADT, especially IADT3, for men without metastases. Based on what I've studied and observed from my layman's perspective, including talks with fellow survivors on ADT, I am convinced they are right.

Once again, I'm seeing that some medical oncologists with practices dedicated to prostate cancer are well ahead of the field. Based on their recommendations over the past decade, I thought continuous ADT for most metastatic patients was well accepted. Now, reading reactions of experienced and able doctors who were surprised by this finding at the ASCO conference (American Society for Clinical Oncology), I am myself surprised that this was not already known. On the other hand, the experts I've been following were basing their convictions on their own clinical experiences and understanding of the nature of the disease rather than on solid evidence from a largea and well done clinical trial. It helps to have research to back up what the experts have been advising.

I am also, once again, surprised that many able doctors are glossing over the crucial distinction between men with and without metastases. I've read of some doctors treating this study as evidence that intermittent ADT is not at least as effective as continuous therapy in men who are not metaststic. That is not at all what this trial was about, as all the men in the trial had metastatic prostate cancer. Moreover, accumulating evidence I feel is persuasive, along with high-level endoresements, indicates that intermittent ADT is superior for many men. I'm thinking the endorsements specifically cover non-metastatic prostate cancer, but I'm not positive.

Here's another key point stemming from my own experience, a published paper and comments from expert medical oncologists whom I follow closely, the point relating mainly to triple ADT: patients whose PSAs drop below 0.05 on triple ADT usually do much better than patients whose PSAs do not go that low. These experts are not usually satisfied with ADT as sufficient therapy if the PSA does not drop below 0.05; they will alter the approach. That may mean keeping the ADT, perhaps with a different mix of drugs or dosages, but it may often mean adding another therapy element. That could be a drug such as Leukine, or Provenge, or one of the new drugs if the patient is eligible for it. In the trial this thread is about, all patients had to have what was considered a good response to ADT. However, rather than achieving a nadir of <0.05, all they had to achieve was a decrease to a PSA of <= 4.0. I suspect most of the metastatic patients in the study would have had trouble getting their PSAs to <0.05, though, with triple ADT and the new drugs now on the scene, I think they would have had a better chance.

I suspect that a few men with metastatic prostate cancer are able to get their PSAs below 0.05, along with other tests and signs indicating the cancer is under control, and that perhaps would open an opportunity for intermittent therapy, or at least a shift to a lighter regimen, such as dropping the LHRH-agonist drug that causes most of the side effect burden.

Regarding orchiectomy and intermittent ADT, the experts I've referred to are actually comfortable with prescribing TRT (Testosterone Replacement Therapy) for appropriate patients with diligent monitoring. I'm not sure how often this is done.

Any questions?

Take care,

Jim

 
Old 06-07-2012, 10:46 AM   #5
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Re: Intermittent hormone therapy inferior to continuous therapy ?

I, too, was reading about this after a friend told me she had read about this on another website. I also read that the trial was done with metastatic patients only.

I guess, then, I question what would be considered "metastatic"....Would it include a patient who has micro-metastases which aren't picked up with standard scans? In other words, if a patient has recurrence or remaining cancer after surgery or radiation, could that be seen as possible metastasis?

To update a little with our personal case, Irv had his appointment with Dr. Myers on May 30th, and not surprising, he believed that Irv should not have had the surgery. At any rate, what's done is done. Now, after a year on hormone therapy, we have doubled up Irv's Avodart which has helped to bring down the DHT by 25%. It's still too high but we'll wait and see if it drops more or we may have to consider increasing the dosage further. He is also starting Irv on 200 mg of Celebrex twice a day and Losartan to increase the flexibility of his arteries.

We already had an appointment with our GP who had concern about the dose of the Celebrex as it could cause irreversible kidney damage and he felt that the Losartan might bring Irv's blood pressure down too low and cause dizziness.

Dr. Myers' response to these concerns is that it takes 18 months for the Celebrex to damage the kidneys and it's a slow process and that's why his creatinine will continually be tested on a monthly basis. I'm not sure what medication would be considered next if he still requires the Celebrex to control his cancer. Dr. Myers also suggested that he cut the Losartan dose in half first to see if it causes dizziness.

The goal is to try and arrest the cancer so that Irv extends his time off the Zoladex and Bicalutamide.

The biggest disappointment for me was finding out that surgery activates the cancer on a permanent basis. I was hoping that this would just be the case during the healing process, due to the increase of blood suppy to the area at that time. I was also concerned to find out that the Gleason score can change over time, meaning that what might have been a 7 (3+4) right after surgery, could mutate to a higher grade over time.

Any comments on what I've written above would be appreciated. What have your experiences been like on Celebrex, if you've ever been on it. I know, Jim, that you're on it now. Have you ever had concerns about how the drug is effecting your kidneys?

I'll look forward to hearing back.

Last edited by honda50; 06-07-2012 at 10:51 AM.

 
Old 06-07-2012, 12:28 PM   #6
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Re: Intermittent hormone therapy inferior to continuous therapy ?

Hi Rhonda,

I hope you're feeling more confident after your meeting with Dr. Myers, and am glad that doubling the Avodart dose had a good effect for Irv.

You asked:
Quote:
I guess, then, I question what would be considered "metastatic"....Would it include a patient who has micro-metastases which aren't picked up with standard scans? In other words, if a patient has recurrence or remaining cancer after surgery or radiation, could that be seen as possible metastasis?
All the patients in the study had metastatic stage IV prostate cancer and a minimum pretreatment PSA level of 5 ng/mL who were proven to be hormone responsive, achieving a PSA below 4 after initial therapy. They were all M1, and any number of known bone metastases were allowed, as were metastases to the liver, brain, or lung. M0 (no distant metastases) and MX (cannot evaluate distant metastases) were not included.Those with no evidence of spread beyond the pelvic region did better with continuous therapy.

I have a good friend, who failed prostatectomy and salvage radiation and has 2 local bone mets, and is under Dr. Lam's care who is now agonizing over the trade-off between quality and quantity of life. It's not an easy decision.

Did you call Dr. Myers after the study was released to ask him how he thought these new findings might impact Irv's treatment plan?

- Allen

 
Old 06-07-2012, 02:30 PM   #7
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Re: Intermittent hormone therapy inferior to continuous therapy ?

Hi Allen,

Thank you for your feedback. We haven't asked Dr Myers' opinion regarding this matter as he actually felt that he wouldn't have even started Irv on hormone therapy in the first place. His goal, now, is to try and arrest the growth of the cancer with the goal in mind being that Irv never has to go back on hormone therapy again. In this regard, I feel very realistic and don't have high expectations of that, but, obviously, Dr. Myers' would probably not agree with the idea of Irv going back on the hormone therapy at this point, as his PSA is still undetectable, as of the last check and his testosterone was still castrate level. Furthermore, Irv never had any detectable mets, so, hopefully, this is the best option for him.

Rhonda

 
Old 06-07-2012, 05:31 PM   #8
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Re: Intermittent hormone therapy inferior to continuous therapy ?

CELEBREX & PROSTATE CANCER

Hi Rhonda and fellow Board participants,

I'm responding to your question about Celebrex at the end of post #5 dated 06-07-2012, 01:46 PM.

I have been meaning to share my experience with Celebrex for prostate cancer, and your question gives me a timely opportunity. It is such an important subject that I feel it deserves a thread all of its own. I started that thread earlier this evening.

I suspect most of us are like I was some years ago, surprised to learn this drug has a role in prostate cancer therapy, though recent results from the STAMPEDE trial throw doubt on the drug's usefulness, suggesting that at most it does not play a major role. (I have found so many flaws in the design, execution or interpretation of clinical trials that I would like to have time to give this trial a thorough look before I personally accept the findings.)

I hope others will share what they know and have experienced with Celebrex, as well as questions.

Take care,

Jim

Last edited by IADT3since2000; 06-07-2012 at 05:33 PM. Reason: Typo.

 
Old 06-07-2012, 05:59 PM   #9
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Re: Intermittent hormone therapy inferior to continuous therapy ?

Hi Allen and Rhonda,

Here are thoughts regarding points each of you raised.

Allen - I'm responding to your recent post where you thought the recent trial findings might apply to Irv. Rhonda has already replied with the key point that Irv is not considered metastatic, but take a look at my post #4 where I've tried to explain this. While some reporters and even doctors have confused the applicability of the findings in this trial, mistakenly thinking they applied to men without mets as well, that is clearly not the case! I'm thoroughly convinced it would be a huge, potentially very costly mistake to undervalue intermittent hormonal blockade in a man who does not have metastases.

Rhonda - Allen thoroughly described what it meant to be metastatic in the particular trial regarding continuous versus intermittent androgen deprivation in metastatic men, and of course I noticed your answer. But you are really asking a broader and penetrating question. Here's my own short answer after considering this question for myself: there are at least three classes of metastatic prostate cancer patients as far as staging goes. The oldest class includes all men with metastasis confirmed by surgery or conventional scans, especially conventional bone and CT scans. The emerging class includes men who would not have been identified by those scans, but whose mets are identified by new scans such as the Na F18 PET/CT bone scan, the C11 choline PET scan, and the Feraheme USPIO high resolution MRI scan. It's important to keep in mind that published research on metastasis does not apply well to this second group, a group that would count as non-metastatic in published research up until now. The third group is men with micro-mets in areas that are not picked up by any scans. Hopefully that latter group is very small. This is a topic that could have a thread all its own.

Take care,

Jim

 
Old 06-13-2012, 08:47 AM   #10
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Re: Intermittent hormone therapy inferior to continuous therapy ?

Regarding the model of cohorts included in the clinical trial with references to this study, they pertain to patients whose cancer has been diagnosed through biopsy (at primary and secondary tumors). In any case, stage IV classification by the American Joint Committee on Cancer (AJCC) Staging, relate to groups of: T4, N0, M0, Any G; Any T, N1, M0, Any G; Any T, any N, M1, Any G. T4 stands for “Tumor is fixed or invades adjacent structures other than seminal vesicles: bladder neck, external sphincter, rectum, levator muscles, and/or pelvic wall.

D2 staged cases are defined by the American Urologic System Stage Grouping (AUSSG) which includes only metastases at distant lymph nodes, metastases to bone or visceral organs.
In other words, these may refer to systemic cases diagnosed after surgery and confirmed in the pathological report. Patients with micrometastases or oligometastatic cancer in regional lymph nodes may have existed but were not included because these cancers could not be identified by earlier type of scanners.

A point of interest is that the number of patients diagnosed on stage IV through surgery before being included in the study has been only 20% of the total number of participants. The rest 80% seem to be patients diagnosed solo through biopsy and other methods (maybe positive CT, MRI, PET, PAP, etc.)
As Jim comments, this cohort would be bigger if diagnosed by present methods in image studies.

Dr. Myers has posted a video speaking about his opinion on the study at his home page (Ask Dr. Myers, Continuous V IHT for PCa).

Here are links to the base data of trials;
http://clinicaltrials.gov/ct2/show/NCT00002651?term=continuous+AND+intermit tent+hormonal+therapy+with+zoladex&rank= 2

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2684851/

Baptista

Last edited by Baptista; 06-13-2012 at 08:54 AM.

 
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