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Cancer: Prostate Message Board

Cancer: Prostate Board Index

[COLOR="DarkGreen"]Hi Rhonda,

I'm so sorry you and Irv are running into this strong headwind at this time. :( Keep your spirits up! I believe you will find a supportive doctor. What you are encountering is what I and many of us have also been faced with, and my impression is that most of us have found a way to get triple blockade. There are at least three strong factors involved: blinders worn by expert research physicians at major institutions, patient empowerment, and limited published medical evidence. There are solutions, but they are not always easy to find. I'll insert some comments in green.[/COLOR]
[QUOTE=honda50;4693686]The world reknowned Dr. Tannock refused to prescribe it. He said that he wouldn't have recommended starting the hormone therapy yet either, but rather would have monitored how fast the PSA goes up for awhile.[/QUOTE]

[COLOR="DarkGreen"]He is not alone in that view. For example, some of the leading doctors at the world famous Brady Urological Institute at Johns Hopkins University, including famed pioneer prostate cancer surgeon Patrick Walsh, share that view. However, many medical oncologists - the doctors who are the experts in drugs for cancer, do not believe in delaying hormonal blockade; all of the experts I follow closely believe that early treatment is clearly superior.[/COLOR]

[QUOTE]He prescribed the Lupron and he believes in intermittent hormone therapy, but just the single blockade....get off the Casodex after 3 weeks and just do the Lupron shots.....3 times...over 9 months....and then stop and wait for the PSA to go up as high as 5 or 10.[/QUOTE]

[COLOR="darkgreen"]That surprises me because there is such compelling evidence in favor of combined blockade and Dr. Tannock clearly is a senior and respected researcher. On the other hand, I've found, to my initial surprise, that major institutions can become locked into certain approaches while locking out other approaches; I suspect this is what is happening with Dr. Tannock. Unlike triple blockade, hormonal therapy with two drugs - an LHRH-agonist (or surgical castration) plus an antiandrogen, has a lot of supportive research.

I just did a search using this search string: " prostate cancer AND combined androgen deprivation therapy "; that yielded 532 hits - clearly a lot of research touching on combined blockade! Here is the citation for hit #9:

"Cancer Sci. 2011 Jan;102(1):51-6. doi: 10.1111/j.1349-7006.2010.01774.x. Epub 2010 Nov 22.
Combined androgen blockade for prostate cancer: review of efficacy, safety and cost-effectiveness.
Akaza H. Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan. The abstract indicates it is a good review of research that has been done. The abstract also mentions that research in the 1990s on combined blockade, was more ambiguous about benefits versus side effects, with that picture improving when Casodex (bicalutamide) came on the scene.

I have been strongly impressed by another Japanese study where the same author just cited is the second author listed. Here's the citation, and there's a free link to the entire study on
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.

Hinotsu S, Akaza H, Usami M, Ogawa O, Kagawa S, Kitamura T, Tsukamoto T, Naito S, Namiki M, Hirao Y, Murai M, Yamanaka H; Japan Study Group of Prostate Cancer (J-CaP).
Jpn J Clin Oncol. 2007 Oct;37(10):775-81. Epub 2007 Oct 26.
PMID: 17965423 [PubMed - indexed for MEDLINE] Free Article

This study also has great graphs that serve to portray the results. The study essentially compares various kinds of hormonal therapy: an antiandrogen alone (1,513 patients); surgical castration alone (955 patients); an LHRH agonist alone (3,015 patients); an LHRH agonist plus a short course of an antiandrogen - the approach Dr. Tannock intends (1,658 patients); surgical castration plus an antiandrogen (a form of combined therapy) (1,001 patients); an LHRH agonist plus an antiandrogen - not short term AA (10,434 patients); watchful waiting (37 patients (I'm not sure why this group was included here); and "other" (796 patients). One of several things I really like about this study is that there are many patients in the various groups.

Figure 1 is a bar graph of the number of patients in each approach, and the LHRH agonist plus long term antiandrogen use is the dominating group. This is, of course, the most common type of combined blockade. Table 1 on page 777 gives information about the patients - type of hospital, age at diagnosis, PSA at diagnosis, and Gleason score, all separated in columns for 2001, 2002, and 2003, the year each patient was registered in the study. There are many other informative tables and figures.

Howeer, I feel that Figure 6 for Stage III is one of the most informative. While four of the approaches notch success marks ranging from 41% to about 43% freedom from progression of the cancer at the five year mark, :) with the surgical castration plus antiandrogen scoring a surprisingly high 70% success at that point :D, the LHRH-agonist monotherapy arm falls practically off the chart right after the five year point, moving from about 39% success to about 12% success within a couple of months! :eek: :dizzy: :( While the approach Dr. Tannock is offering is above 40% at about the four years 8 months point, that is the last follow-up shown on the chart, and it is falling rather steeply.

It's important to understand that all of these approaches involve continuous, not intermittent, hormonal therapy, and none of the approaches in Figure 6 involve triple blockade. My strong impression is that patients on intermittent triple blockade, like me, typically do much better!

I just did the same search you see above but turned on these filters with the Limits button: only items with abstracts, Humans, Clinical Trial. That cut down the results to 112. (It's hard for me to do this because I always see interesting titles that I would like to explore.) I then removed "radiation" by using this string: " prostate cancer AND combined androgen deprivation therapy NOT radiation ", with 68 hits as the result. This demonstrates that there are many studies with results for combined blockade, and you will probably find some useful and encouraging information in them. Just bear in mind that these studies were done with patients treated in the past, and the more in the past, the fewer advances in technology, such as intermittent treatment, especially with triple blockade.


[QUOTE]I think of a tree taking route and letting the routes flourish and gain strength and momentum.[/QUOTE]

[COLOR="DarkGreen"]Yes. That's what we need to prevent. I can understand LHRH-agonist single drug therapy, perhaps with a short course of an antiandrogen, as preparation for radiation, but it no longer seems sound to me for a long-term approach.[/COLOR]

[COLOR="darkgreen"]He is dead set against triple blockade and feels that the added toxicity is no good without any evidence that it helps. He says he's had patients who have also lived for more than 10 years on his medication protocol.[/COLOR]

[COLOR="darkgreen"]It's so unfortunate that doctors do not bear in mind that 95% of high-risk patients, at least in the US, are alive at the ten year point; having your patient alive at that point is not such an accomplishment. What [I][U]IS[/U][/I] impressive is patients like me who are still doing very well and responding to hormonal therapy at the ten year point! :cool: Fortunately, that is typical for many of us on intermittent triple blockade, with lower-risk and intermediate-risk patients often able to do it with just one course of triple blockade.

As for the added toxicity, well, growing more hair in the male-pattern-baldness areas is something most of us are capable of enduring! ;) (Of course I should also mention better urination behavior for those of us who still have prostates, another of those tough side effects. ;)Finasteride and Avodart are very mild drugs for most of us. One leading doctor with a heavy practice in triple blockade has stated that finasteride and Avodart add almost nothing to the side effect burden. What Dr. Tannock's statement really shows, unfortunately, is that he is not familiar with the way these drugs act in a triple blockade (or even antiandrogen plus 5-ARI drug) approach. Hopefully he will gain that knowledge and change his opinion someday.

As for his statement that "there's no evidence it helps," you know the answer to that: yes, there is some evidence, including evidence in a major, peer-reviewed journal, but it is unfortunately quite limited outside of less formal publications.[/COLOR]

[QUOTE]He wouldn't hear of what I had to say about Dr. Scholz, Dr. Strum and Dr. Myers and even went as far as saying that one is way on the outer edge and that it's dangerous.[/QUOTE]

[COLOR="darkgreen"]I've run into this myself more than once from prostate cancer research experts at major institutions. The first time was during a consultation with Dr. Mario Eisenberger at Johns Hopkins, just after I had finally started taking finasteride, giving me a triple blockade approach about ten months after diagnosis. Dr. Eisenberger has an international reputation, especially in chemotherapy for prostate cancer. He advised me to dump the remaining Proscar (finasteride) in my container, and he was dismissive when I tried to tell him what the experts were saying. He knew Dr. Myers well from his days at the National Institutes of Health, but he thought he had become a loose cannon, a doctor operating beyond the fringe. Several years later I presented a survivor statement at an FDA committee hearing on a drug, and I approached Dr. Eisenberger afterwards. I doubt that he remembered me, but I mentioned our consultation and told him of my great success on triple blockade. He did not want to hear of it.

The other instance was with Dr. Christopher Logothetis of MD Anderson, also a prostate cancer medical oncologist with an international reputation. Dr. Logothetis too was dismissive when I talked to him after a "Meet the Experts" session at a cancer researchers conference, where I was again representing survivors. I again had a powerful sense of the "If I did not invent it, it doesn't count" syndrome. Both of these doctors, and some (but not all) others from major institutions, were highly resistant to research not performed in a major university setting but performed instead by doctors in private practice. [/COLOR]

[QUOTE]I mentioned the clinical trial done by the PMH specialists and he said that it's different because those men had very low risk, slow growing cancer.[/QUOTE]

[COLOR="darkgreen"]Actually, such patients were among the early patients treated with triple blockade many years ago by the doctors who are now experts. They saw the stunning success of such patients, and gradually they expanded their willingness to offer triple blockade, eventually making it their primary approach. Dr. Tannock is on that road, I think, but unless he learns of the work done by the experts and credits it, it will probably take him years before he freely recommends triple blockade.[/COLOR]

[QUOTE]Not sure where we go from here....He just thinks it's very unwise for patients to decide on their own treatment and would be much smarter to follow what the doctors recommend.[/QUOTE]

[COLOR="darkgreen"]Here you are running smack into the docile patient versus empowered patient divide. Many doctors want docile patients, though they prefer them to have basic information. My first three urologists were all like that, and all were respected, able doctors. I appreciate what the latter two did for me in providing information and orientation, but they were not what I needed.

In sharp contrast, the doctors I follow are committed and dedicated to patient empowerment. The books "A Primer on Prostate Cancer", "Beating Prostate Cancer: Hormonal Therapy & Diet", "Invasion of the Prostate Snatchers", the Prostate Forum Newsletter, the publications of the Prostate Cancer Research Institute including its Insights newsletter, and the National/International Conferences on Prostate Cancer are some of the examples of workings of the prostate cancer patient empowerment movement.[/COLOR]

Well, that's the update. Comments are welcome.[/QUOTE]

[COLOR="darkgreen"]Here are some thoughts on getting on triple blockade. You might have success in finding a local Toronto medical oncologist in private practice, who is open minded and not associated with a university. (That's what I finally did.) Dr. Fernand Labrie or the experts in Vancouver might be able to recommend such a doctor. I'm going to a research conference in early March as a survivor representative, and I'll see if I can get some names in the Toronto area from one of the Vancouver researchers who are sure to be there. However, you and Irv could probably reach them sooner by phone. (At least you are covered for three months of combined blockade.)

You also might want to approach Dr. Klotz again. He too may suffer from the major institution blinders, but he has a superb mind and is a pioneer who is able to take criticism from his peers in stride and take risks. He also is more than well aware that conventional wisdom in medicine is often wrong. (For instance, I'm sure he took a lot of heat when he recommended that active surveillance was suitable for appropriately qualified patients of [I]any[/I] age; he is probably still catching flack for that view. Fortunately, he has the research facts to back his claims.) He was at the last session of the conference I will be attending, and I might get a chance to ask him if he is present.

Another option would be to travel to Vancouver for a consultation or to Quebec to see Dr. Labrie. Some doctors at Vancouver are expert in combined blockade and intermittent therapy, and Dr. Labrie is, of course, expert in combined blockade, and I think he has moved on to triple blockade; it might be possible to get them to start Irv on triple blockade with the understanding that a local doctor would administer the shots and do local testing. Each of the US experts has patients they support in this way.

As always, I hope you find something that works for you.

Take care,

Jim :wave:[/COLOR]

[COLOR="DarkGreen"]Hi Rhonda and Allen (and all of us who are interested),

Thanks for that citation in your post #6, Allen. It's on my list to check - kind of overwhelmed these days.

I'm responding mainly because there is an important understanding to convey about the role of finasteride, and your post #6, Allen, reflects a different and less encouraging view that is very common among doctors with whom I have talked who are not expert in hormonal therapy. (I have not talked to him, but that group also includes the justly revered Dr. Patrick Walsh of Johns Hopkins. We need to remember that we revere him for his surgical pioneering, surgical research, and his peerless dedication, but not for his knowledge of hormonal therapy, which has at least one gaping hole in understanding.)

I'll insert some thoughts in green in an excerpt from your post.[/COLOR]

[QUOTE][COLOR="darkgreen"][Your question to Rhonda][/COLOR]But have you seen any study that shows that a triple blockade is any more useful than what Irv's doctor recommends in a case like his, and if it is, is the marginal benefit worth pursuing doctors all over Canada for?[/QUOTE]

[COLOR="darkgreen"]First let's talk about what Irv's doctor is planning. He is proposing a short course of antiandrogen and continuous LHRH-agonist medication for Irv's case that clearly has some challenging characteristics.

That course of therapy has a good chance of working for a limited number of years for someone like Irv; when you look at the Japanese study of hormonal blockade mentioned earlier in this thread, it appears that around 40% of patients of stage III patients do well up to five years, with 60% recurring before that. Looking at the graph, I suspect that percentage of success will fall rather steeply after the five year point. Actually, the trend line is falling at a clearly steeper rate from around 67% success at nearly the four year point to around 43% as the patient approaches the five year point. While this Hinotsu ... Yamanaka study from 2007 is just one study, the results strike me as similar to what I've seen repeatedly in looking at studies for hormonal blockade. Believe me, I've looked at such studies as if my life depended on it, so it's not a casual interest.

On the good side, even after such blockade fails, a study I find credible (Oefelein, Aggarwal and Resnick, Wayne State U.) indicates that survival after failure averages (median) 40 months for men with bone mets at the time of failure and 68 months for men without bone mets at that time. (This is not recognized by many doctors as they unfortunately use studies for their views that are based on artificial, later points from which they count survival. I can explain if anyone wants to read about it.) Therefore, you can project a decent shot at 5 years of success on blockade plus about 4 or 5 years more of survival from this time. That gets us to around the ten year point or more for about half the patients, with about half not living that long. Moreover, those figures are for men treated quite a few years in the past, and survival now would almost certainly be considerably better.

Okay, now lets' look at triple therapy, involving finasteride, though today the experts prefer Avodart as the third element for most men. Your point about the shortage of formal, peer-reviewed, published medical studies is a good one, unfortunately. However, there is at least one publication in a major journal for double blockade with finasteride maintenance (Scholz, Lam, Strum and colleagues), and there have been several impressive poster presentations at conferences. The Primer has documented preliminary research comparing triple with combined (two drug) blockade. Several leading medical oncologists who specialize in prostate cancer have stated their strong preference for triple blockade in challenging cases. There is a multitude of patients like me (most with less challenging cases) who have done very well on intermittent triple blockade with maintenance. A clinical trial is now in progress to test whether adding Avodart can restore success to men who are failing after combined blockade (Dr. Oliver Sartor). What this feels like is the grass roots revolution that is now occuring in the Arab world.

You are visualizing the benefit of adding finasteride as marginal, if there is even any benefit. (Of course, Irv's doctor is not planning continuous antiandrogen therapy; but that shortcoming should not be difficult to overcome as such continuous therapy is a staple treatment among medical oncologists and even many surgeons who manage blockade.) So are many doctors visualizing it as marginal who are not that familiar with advanced hormonal therapy. In sharp contrast, I am convinced that we would not be seeing the excitement that we are seeing in the survivor community and among leading doctors for marginal benefit. The graph for a small study in the then Strum-Scholz practice gives us a tantalizing view of what we think is the power of intermittent (or one time) triple blockade with finasteride maintenance. The chart is Figure 60 in my original edition of the Primer, and it's titled "IAD3 versus IAD2 (PSAR Patients [meaning those whose cancer had recurred after surger, radiation, or both] - Comparison of Time to Reach Biological Endpoint". The goal was to keep coasting until reaching a therapy restart point after stopping the heavy duty drugs - the ADT2 part of ADT2 and ADT3. In other words, the goal was for the patients to have as long a vacation as was thought reasonable at that time.

The end of the race was set as a rise in PSA to 5.0 for the IADT2 group, but to just 2.5 for the IADT3 group. That handicap was done because it was thought at the time that finasteride might be [I]artificially[/I] lowering the PSA by half, which, if true, would make 2.5 comparable to 5. (Now it is believed that there is actual benefit to the patient from the lower PSA achieved by the 5-ARI drugs finasteride and Avodart.)

Okay, time for results: The graph shows the IAD2 patients gradually needing to restart therapy as results were tracked for up to about 77 months. The ever-useful median point for restarting therapy - half doing better, half not as well - occured at 24 months for the IADT2 group (though 25% managed to coast for over five years, with the last patient making it to the 77 month point (eyeballing these months from the graph). In happy contrast, the IADT3 patients had a slower rate of declining success, with more than half still not needing to restart therapy at the 60 month point ([I][U]FIVE YEARS![/U][/I]). It looks like about 55% or so were still successful at that point, and the results from 2000, perhaps updated to late 2001 or 2002, were not published for longer follow-up. Also, those who were not "successful" on this graph were not failures in the sense that hormonal therapy was not working; instead, like me, their "lack of success" with one round of triple therapy simply meant that they needed to initiate another round, with [I]at least[/I] several successful rounds typically possible.

The bottom line:

IADT2 - 50% of men needed to restart therapy by the two year point (24 months)

IADT3 - more than 50% of men were still enjoying a vacation at the five year point (60 months).

To those of us whose options have been narrowed down to hormonal therapy, results like that are enormously encouraging! :D :angel:

The Scholz - Strum - Lam series of patients continues to be studied, and I'm confident we will see further results at some point.

The Tucker, Leibowitz, Roundy presentation to a special joint meeting on prostate cancer in Orlando, 2005, also has some highly encouraging results, but the authors are still struggling to tie down details of patient follow-up that will meet the standards for publication in a major peer-reviewed publication. I'm dearly hoping they succeed, as the results indicate stunning success. :eek: :dizzy: :D However, the group they discuss has not had prior therapy; they are patients who elected to go straight to maintained triple hormonal therapy despite having low-risk cases in many instances. It is important to remember that doctors can become overenthusiastic about their results, perhaps overlooking the failures that need to be counted as well as the successes; the peer-review publication process, though not perfect, is good protection to make sound data more likely. That's why I really want to see that formal publication of results from this series.[/COLOR]

[QUOTE].... I agree that finasteride has minor side effects, and if I were the doctor I would definitely have given you a scrip for your peace of mind if nothing else... If the RT is a cannonball [COLOR="darkgreen"][later clarified that Irv is not a candidate for RT][/COLOR], the finasteride is a flyswatter. I think one has to pick one's battles. [/QUOTE]

[COLOR="darkgreen"]Here is a really key concept: finasteride is just a flyswatter in some approaches, though that is probably all some men need to boost their odds of success. I use finasteride when I go off the heavy duty drugs, during my vacation period, based on the now published research (Scholz, Strum, Lam and colleagues) that shows markedly longer vacation periods for men using a 5-alpha reductase inhibitor drug (finasteride or Avodart) during the vacation period. I'm convinced I'm experiencing greater success with finasteride as maintenance, but, it's also very clear that finasteride alone is not sufficient to hold back my prostate cancer. In fact, toward the ends of my vacations, the cancer is roaring back at a short doubling time of around five months. At this point the finasteride is more like the flyswatter. It's like facing the bully alone after your big, strong brother has gone elsewhere.

However, [I][U]used in combination with an LHRH-agonist and an antiandrogen, finasteride or Avodart create a [B]synergy[/B] that is powerful! :angel:[/U][/I] Here's how we think it works, based on a combination of animal, lab and human prostate cancer research. While adequately done use of an LHRH-agonist stops all testicular production of testosterone that fuels the cancer and converts to the more potent DHT fuel, and while antiandrogens like bicalutamide block the androgen receptor fueling ports to some extent for the indirectly (not by testes) testosterone and DHT, bicalutamide does not tightly grip those fueling ports. In fact, if there is DHT around, the DHT often muscles out the bicalutamide, and thereby the fueling of the cancer cells continues. (The new drug Abiraterone, not yet approved, appears to do a basically similar job in a better way, but that's another story.)

Enter lowly finasteride, or lowly Avodart. They don't block the androgen receptor, the cancer cell's fueling port. Nor are these lightweights any good at stopping testicular production of testosterone. [I][U]But, they are very good at drastically reducing the amount of DHT that is produced from testosterone! Voila![/U][/I] :D Therefore, the thinking is that, by reducing the DHT that otherwise would successfully compete with the bicalutamide, the otherwise lowly 5-ARI drugs make the bicalutamide (antiandrogen) arm of blockade far more successful! :angel:

Fly swatter no more!

Take care,

Jim :wave:[/COLOR]

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