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Old 01-22-2009, 05:40 PM   #1
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Smile So far so good, 2nd PSA, third round, tenth year IADT3

I'm delighted and relieved to report that my PSA again declined this time from 2.27 in November to .86 on January 16th as I complete the fourth month and move into the fifth month of triple hormonal blockade with Lupron (four month shot for me, = 30 mg), Casodex (50 mg/day for me), and finasteride (2 X 5 mg/day). Intermittent triple hormonal blockade is also known as Intermittent Androgen Deprivation Therapy 3; it's abbreviated as IADT3.

This is following up on the thread I started on November 27, 2008, entitled "So far so good - first PSA, third round/ninth year IADT." Here is the key information I reported then: "... My PSA dropped nicely to 2.27 on November 12 from 9.53 on September 3 at about the two month point since stopping thalidomide (September 17) and resuming Casodex (September 18) and then Lupron (September 26) . (I'm on 10 mg of finasteride continuously, plus Boniva for bone density, simvastatin to lower the risk of lethal prostate cancer plus heart health benefit, and a supportive program of diet/nutrition/supplements, exercise, and stress reduction.) ..."

My goal is to stay on blockade for at least a year and to get that PSA below 0.05. Unlike many patients who get below 0.05 within a few months on triple blockade, it has taken me many months on the two previous cycles. But I've gotten there twice before (in fact, to <0.01 twice before), and that's most important, and the unusually long time to get there is not surprising considering my highly challenging case.

I see this current continued decline as very good and encouraging progress, but I am slightly concerned that I was able to cover about the same ground in two and a half months during my second cycle of blockade, and it took me four months this time. As far as I know that is not a big deal, but it could be a clue that the cancer has become a bit more difficult to deal with; it could also be the result of departing from my routine over the Thanksgiving, Christmas, and New Year season. (It took me about six months to cover the same ground during my first cycle, but I was on only two drug blockade at that time - Lupron and Casodex without the finasteride.)

On the other hand, I'm enjoying a lighter experience of side effects this time, especially hot flashes. The flashes and sweats for me were quite tolerable for the first cycle, better for the second, and not bad at all this time. That's fairly typical as older men usually have an easier time with the side effects, and I'm now nine years older than when I started.

Well, no more PSA tests for another two months, and no more Lupron shots for another four months! (I've got to add that that last shot on January 16 was not bad at all; the nurse gave it high up in the butt muscle, and there was almost no soreness. )

Jim

Last edited by IADT3since2000; 01-22-2009 at 05:43 PM. Reason: Explained abbreviation "IADT3" within minutes of posting.

 
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Old 01-22-2009, 06:03 PM   #2
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Re: So far so good, 2nd PSA, third round, tenth year IADT3

Jim- You are most definitely an inspiration to so many of us-- we generally don't realize how complex this road can be for some. Your ability to have learned so much about this disease and to tackle things head-on is truly remarkable. Best continued success in managing all this, and without ever having had surgery or radiation, the two things we seem to talk most about on this board. And now I finally know the meaning of your screen name...

 
Old 01-31-2009, 12:24 PM   #3
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Smile Re: So far so good, 2nd PSA, third round, tenth year IADT3

I'm very pleased for you Jim. You definitely deserve it for all your research and the help and encouragement you give everyone on here.

All the best, T.
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Peter, Brachytherapy in Guildford, England March 2008

 
Old 02-02-2009, 05:52 AM   #4
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Re: So far so good, 2nd PSA, third round, tenth year IADT3

Hi Jim. I wonder what happens to the cancer cells or tumors and to the prostate itself when your psa gets to .86 or lower. Are they still there but inactive or do they actually disapear. If you were to have a biopsy at this time I wonder what it would show? Maybe you know the answer. Also, if I'm not being to personal, I wondered if you have ever had a bone scan or any bone pain related to your cancer. It's something I deal with on a fairly regular basis. I talked to my oncologist about triple blockade therapy and he was not really enthusiastic about the treatment. He told me that in the late 80's when he was in residency, it was a new and promising treatment, however he believes the statistics show no better sucess overall with triple blockade than just taking a single blockade. I'm meeting with my urologist soon and I'm going to question him as to his views on this protocall. With the sucess you have had I see nothing to lose for myself to try a triple blockade and then measure results. I was diagnosed 6 years ago with metastatic pc. Thanks for all your information on this board and contiinued good sucess. Dave

 
Old 02-03-2009, 02:46 PM   #5
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Re: So far so good, 2nd PSA, third round, tenth year IADT3

Hi Dave,

I hope you are doing well. I'm inserting some comments in green in an excerpt of your post from yesterday. Jim


Quote:
Originally Posted by dustydigger View Post
Hi Jim. I wonder what happens to the cancer cells or tumors and to the prostate itself when your psa gets to .86 or lower. Are they still there but inactive or do they actually disapear. If you were to have a biopsy at this time I wonder what it would show?

For me, and probably for many of us, it seems to take around nine months or perhaps more to get the maximum killing of prostate cancer cells. While many are killed, it is thought they are mainly cells that are not the root of the trouble, those cells being "prostate cancer stem cells." I have only been on blockade in this third round for about four and a half months in this third round, so its likely that that early drop in PSA is due to a sharp decline in PSA production by prostate cancer cells that still exist but can no longer produce much PSA, spread, or cause trouble, at this point. That's what happens in the early months: loss of PSA production.

I have only had one biopsy, the one back in December of 1999. However, some other patients on intermittent triple hormonal blockade with maintenance have had follow-up biopsies. For patients who are still responding well to blockade, my impression is that the biopsies show the cancer is still there but much diminished while on blockade. Previous DREs while I've been on blockade have revealed a prostate so reduced that the urologist said it is "flat."


... Also, if I'm not being to personal, I wondered if you have ever had a bone scan or any bone pain related to your cancer. It's something I deal with on a fairly regular basis.

I've never had bone pain related to the cancer. The doctors I follow closely who are highly experienced in hormonal therapy regularly tell stories of how blockade treatment and associated bisphosphonate drug support markedly reduce or eliminate bone pain for many patients. I've got a further thought on that below.

I talked to my oncologist about triple blockade therapy and he was not really enthusiastic about the treatment. He told me that in the late 80's when he was in residency, it was a new and promising treatment, however he believes the statistics show no better sucess overall with triple blockade than just taking a single blockade.

First, it could be that being on just single drug blockade with an LHRH-agonist type drug (the Eligard for you, Lupron for me) was not enough to sufficiently block the supply of androgens (testosterone, DHT) to the prostate cancer cells. That could be allowing them to grow and create the pressure and pain in your bones. Also, I know that Pamidronate is a fine drug, but Zometa is far more powerful in slowing down, stabilizing or even reducing and eliminating prostate cancer bone metastases. Have your doctors gone over the pros and cons of using Zometa?

Your doctor is not remembering the timing right, which suggests he had other things on his mind, quite understandably, than focusing closely on combined and especially triple blockade. I believe that Dr. Robert Leibowitz of California may have been the first to use triple blockade (Lupron or Zoladex,etc; Casodex or flutamide; and Proscar (now available generically as finasteride, with Avodart as an alternative favored by other experts) with maintenance (finasteride or Avodart), and he did not so treat his first patient until 1990, not reaching his first hundred patients on that regimen until 1999. He and other doctors who are expert in triple blockade were inspired by Canadian doctor Fernand Labrie, practicing in Quebec, who is known as the "father of combined hormonal blockade therapy." However, Dr. Labrie, used only the first two classes of drugs (LHRH-agonist class and antiandrogen class) for most of his blockade and strongly favored continuous blockade, not acknowledging the usefulness of adding finasteride or Avodart until recently. To me this indicates strongly that triple blockade was not on the scene in the 1980s.

I just did a search of [url]www.pubmed.gov[/url] for " prostate cancer AND combined hormonal blockade " and got 226 hits. There was a discouraging report in the late 1980s, which is what your doctor might be remembering, and there have been other unencouraging reports. Incidentally, the "antiandrogen drug used was cyproterone (spelling?) acetate, which has not been approved for use in the US; US doctors commonly use Casodex or flutamide, plus some other less likely options. However, the stage of the disease in the research, especially the extent of metastases, is critical. It turns out that combined blockade, especially triple blockade, is usually quite successful when the patient has no detectable metastases. You can do the same search and look over the abstracts for yourself.

To me, all of this suggests that your oncologist is not overly knowledgable about hormonal therapy and has not kept up with developments. He might be a generally fine doctor, and he would certainly not be alone in being out of touch with expert use of hormonal therapy. But if I were you, I would want either another, more knowledgable doctor or would want to build an understanding with the current doctor about combined and triple hormonal blockade. I'm convinced that many doctors prematurely label their patients "hormone refractory" or "androgen independent" (meaning that hormonal therapy alone is no longer sufficient to combat the cancer). I'm just a now savvy layman, but I've heard experts in hormonal therapy express this view, and it's not hard to understand the key facts.

I don't recall that you ever said whether your doctor had tested for your testosterone and DHT levels after your PSA started rising on single blockade with Eligard. Such testing is really one of the essentials before concluding that a patient is refractory. If the testosterone is not below 20 (some docs would say 50, but not those I consider leading experts), and if the DHT is not below 10 or at least in the low teens, then that's a strong suggestion that the administration of blockade is inadequate rather than that the patient is refractory to blockade. For instance, you may be one of those men whose adrenal glands manage to make up much of the lost testosterone; that can gut a hormonal blockade program and is easily fixable.

Here's a bit of scary news, but it appears to me to be an important clue to how men on single blockade respond, and it can provide the rationale from moving beyond single to double or triple blockade.

First a little background. In the past year I've become aware that my therapy - intermittent hormonal blockade (actually triple blockade with maintenance for me) - is emerging as an important primary therapy, in other words, a therapy used first and on its own! In preparing for posting a thread on this board, I ran across a very interesting paper from Japan on how hormonal therapy is used there. (Preview: they use it as primary therapy far more than we do, in fact using it for 45% of patients according to one record.)

The paper combines six forms of hormonal therapy, including single therapy (either castration or use of an LHRH-agonist drug like Lupron, Zoladex, Eligard, or Viadur), and combined therapy (one of these treatment options plus an antiandrogen drug, such as Casodex or flutamide. They report results for both progression free control of cancer as well as survival for each year through slightly beyond the five year point for various levels of risk in patients' cases.

Here's the key for you: for Stage III (probably not too much better than your metastatic case in view of your success), for progression free survival, single LHRH-agonist drug therapy was not too far from the other approaches until the five year point, but at the five year point the bottom dropped out: while four of the hormonal blockade approaches hovered around the 40% success level at five years, with no dramatic declines, LHRH-agonist single drug therapy plummeted from about the 40% success level at five years to just slightly over 10% success a few months later. This was not due just to a fluke based on a small number of patients as there were initially 484 patients in the LHRH-agonist arm of the study. (By the way, the arm combining surgical castration plus an antiandrogen drug clearly did the best, with 70% success and a flat line for well over a year (meaning no fresh failures during that period) as the patients passed the five year point. But ouch!, and that complicates intermittent therapy. - I'm doing well enough, thank you, and am not ready to go that route! Still I'm impressed! Plus, surgical castration is relatively much cheaper than the drugs!)

They report overall survival for Stage III too, but they combine both medical and surgical castration, and so the results are not really comparable.

Unfortunately results for Stage IV were not that great, either for progression or overall survival, which is a common observation in studies. In brief, for progression, half of Stage IV patients for all of the approaches progressed at roughly the 1 1/2 to 2 year point. I'm sorry to say that overall survival was not great either, with about half the patients not surviving past the four year point. However, the key facts that (1) you have already done better than most of the metastatic patients in that study and (2) that treatments are considerably better now make me think that you have a good shot!

You could check out the Japanese study in [url]www.pubmed.gov[/url]. The citation facts include Shiro Hinotsu, Hideyuki Akaza... Hidetoshi Yamanaka (authors), "Current Status of Endocrine Therapy for Prostate Cancer in Japan - Analysis of Primary Androgen Deprivation Therapy on the Basis of Data Collected by J-CaP," Jpn J Clin Oncol 2007: 37(10) 775-781. Plus, PubMed provides a link to a free copy of the entire paper.





I'm meeting with my urologist soon and I'm going to question him as to his views on this protocall. With the sucess you have had I see nothing to lose for myself to try a triple blockade and then measure results.

Yes, I think you might have success!

I was diagnosed 6 years ago with metastatic pc. Thanks for all your information on this board and contiinued good sucess. Dave
Take care, and please followup with any questions or observations,

Jim

 
Old 02-03-2009, 08:30 PM   #6
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Re: So far so good, 2nd PSA, third round, tenth year IADT3

Hi Jim. I will follow up on the info you have provided. I just want to thank you for taking the time to respond to my post. All the best. Dave

 
Old 02-04-2009, 09:00 AM   #7
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Re: So far so good, 2nd PSA, third round, tenth year IADT3

Hi again Dave,

You're welcome! Glad to help.

I would like to add some more brief points.

I forgot to mention in response to your question that I did have a bone scan within a week of my diagnosis, and surprisingly it was negative. I seem to be one of a relatively few patients who have aggressive cancer that has extra difficulty in metastasizing. Recently a few studies have been done on such patients.

Did you ever learn how many metastases you had? It could matter, as there is growing interest in patients with few mets, say roughly five detectable mets or fewer. Some research has been completed. It seems that the number of mets makes quite a difference, AND, in some cases each can be treated and eliminated with radiation, which seems to help a lot. (We have also known for years now that bisphosphonates, especially Zometa, can stabilize or even reverse bone metastases.) Researchers are using the term "oligometastases" or "oligometastasis" for this situation - now that's a mouthful!

Here are a couple of excerpts from papers that I checked on PubMed about single hormonal blockade being inadvisable in challenging cases. By the way, Dr. Klotz is the same brilliant, Canadian doctor who is arguably the world's leading guru for Advanced Surveillance with deferred therapy.

"Maximal androgen blockade for advanced prostate cancer." Klotz L. Best Pract Res Clin Endocrinol Metab. 2008 Apr;22(2):331-40. Review.

"...In prostate cancer patients at high risk for mortality (based on extent of disease or prostate-specific antigen kinetics), combination therapy with bicalutamide should be considered in preference to monotherapy."

- - - -

"Luteinizing hormone-releasing hormone monotherapy: a viable option for treatment of prostate cancer?" Schellhammer PF. Urology. 2001 Aug;58(2 Suppl 1):10-5.

[Dr. Schellhammer is a very highly regarded urologist in my state, Virginia.]


"... When using monotherapy, it is necessary to recognize several important facts. Castrate testosterone levels are not achieved or maintained in all patients. For some patients this may be a disadvantage. Additionally, before categorizing a patient as having an androgen-independent tumor, it is important to measure serum testosterone to ensure that LHRH analog monotherapy has achieved and maintained a castrate testosterone level."
- - - -

I've seen the points they make made by other doctors whom I consider leaders in prostate cancer hormonal therapy, but usually those doctors are medical oncologists. I believe that both Drs. Klotz and Schelhammer are urologists.

In effect, with single drug (or surgical castration) hormonal blockade, patients have closed the barn door but have left the loft open, and maybe also the back door. That's not good!

One last point about the evidence for and against combined hormonal blockade. There was a "meta study" in the 90s that found little advantage for combined hormonal blockade. "Meta" means it was a review of results from many studies. Unfortunately, it had great influence and still sticks in the minds of many doctors as the last word. I say "unfortunately" because the vast majority of the patients in the studies that were included were already metastatic, and hormonal blockade clearly does not typically work as well in such patients. I still find it odd that well-educated, highly intelligent physicians don't realize there is a key difference in response to hormonal blockade between non-metastatic and metastatic patients, with the non-metastatic patients usually doing very well with hormonal blockade! While that unfavorable record of success for hormonal blockade may seem to apply to you as a metastatic patient, it appears you may well be closer to non-metastatic patients in the way you respond. (However, on the negative side, bone pain is an adverse clue, but only one clue.) Also, as I noted before, treatments, case analysis and decision making have improved a lot since the days of those studies.

Take care,

Jim

 
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