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Cancer: Prostate Message Board


Cancer: Prostate Board Index


Re: Question:
Nov 23, 2011
[COLOR="DarkGreen"]Hi to all who have been participating in this thread, which has raised some important issues. I'll give some thoughts in green, taking off from Allen's post #5.[/COLOR]

[QUOTE=Tall Allen;4883926]Hi Rhonda,

The study didn't compare the new protocol to a triple blockade.[/QUOTE]

[COLOR="darkgreen"]Over the past couple of years I've observed that the researchers involved with Abarelix do not seem to be aware of the work with triple androgen deprvation therapy. That's not too surprising as not much has yet been published about it. Still, it suggests these groups are not communicating.[/COLOR]

[QUOTE]I think the point was that they achieved castrate levels of testosterone without using an anti-androgen and the toxicity associated with that drug.[/QUOTE]

[COLOR="darkgreen"]There are two points here. The first is that the Abarelix researchers used a standard for castrate testosterone of <50, which is standard among researchers. However, the doctors I've been following for years are convinced that the threshold should be <20, and there has been a growing number of doctors who believe that <20 is a much better threshold. For instance, if a man on ADT3 has a PSA that has not dropped far enough and has a testosterone level of 30, they will look to see why the ADT3 is not doing the job of adequately reducing testosterone, while conventional doctors will sit back and not see any issue. Often there is a cause that can be corrected. I'm disappointed the authors of the paper did not use the lower threshold of 20. On the other hand, my impression from the Abarelix reports is that the drug causes a rapid decrease in testosterone and likely would have notched outstanding results if the threshold had been <20. Does anyone know of such a study?

The second point is that anti-androgen toxicity (such as breast enlargement, tenderness and perhaps pain) is much more pronounced when an antiandrogen drug is used without an LHRH-agonist, such as Zoladex. The added side effect burden is much lower when the two classes of drugs are used together. :) [/COLOR]

[QUOTE]It also reduced the surge in Testosterone that occurs when an anti-androgen is added.[/QUOTE]

[COLOR="darkgreen"]I'm sure you meant when the LHRH-agonist was added. The evidence is convincing that abarelix does a great job of eliminating that surge without the need for an antiandrogen, as documented in the study you cited.[/COLOR]

[QUOTE]It may be that the anti-androgen plays a major role in eventual hormone resistance, so the new protocol may work longer, although the test didn't run long enough to determine that.[/QUOTE]

[COLOR="darkgreen"]I have never seen any study that suggests that. It is clear that many of us who take an antiandrogen, even intermittently, will develop a mutation in the cancer that allows the cancer to use the antiandrogne as fuel, but that is not the same as hormone resistance. I may be at that point myself, and, if I go back on triple blockade, I'll be switching antiandrogens to avoid the risk, at least for a while. It's important to keep in mind that many of us can use these drugs, at least on an intermittent basis, for many years before we run into a need to change the approach. I've been on Casodex/bicalutamide intermittently since March of 2000, over a decade ago.[/COLOR]

[QUOTE]Avodart prevents the conversion of testosterone into DHT which is 10x more potent at activating the androgen receptor. The activated androgen receptor triggers growth of both benign hyperplasia and cancerous prostate cells. Seems to me like a good idea to prevent that, especially on the off periods when testosterone production resumes.[/QUOTE]

[COLOR="darkgreen"]I'll add an "Amen" to that![/COLOR]


[COLOR="darkgreen"]Rhonda, in your post of 3:13 AM today, you asked:[/COLOR]

[QUOTE]Also, is the study revealing that Abarelix, followed by the LHRH agonist (like Lupron or Zoladex) is superior to triple blockade androgen deprivation therapy, or is it just an alternative or a form of second line hormone therapy? Would Avodart also be a part of this alternative protocol?
[/QUOTE]

[COLOR="darkgreen"]Here's where I'm going to have to do some studying to get a firm grip on what Abarelix does. The study Allen cited shows that the drug makes testosterone plunge fast without causing a flare in testosterone, but I don't recall evidence that it also blocks the androgen receptors as the antiandrogens do. I'm thinking Abarelix [I]may[/I] block testosterone not only from the testes but also from other sources, such as from the adrenal glands, by indirect routes, and perhaps even from cancer cells themselves. (Testosterone produced by cancer cells is a fairly new finding.) If Abarelix does block all sources of testosterone with high efficiency, because DHT is made from testosterone, Abarelix may make an antiandrogen and finasteride or Avodart unnecessary. If Abarelix does not block all the other sources of testosterone, then it seems to me that patients would benefit from antiandrogens and finasteride or Avodart. [/COLOR]

[COLOR="darkgreen"]Allen - In your 12:46 AM post today responding to Rhonda's question you wrote:[/COLOR]

[QUOTE]The reason Avodart cuts PSA in half is mostly because it gets rid of the effect of BPH on PSA. If you have no prostate gland, you have no BPH. The effect on reducing DHT-fed cancerous production PSA is much smaller. Because of this you may not want to wait for a higher PSA level when you're on solo Avodart therapy.
[/QUOTE]

[COLOR="darkgreen"]I suspect the main problem with Avodart or finasteride as solo therapy is that most of us will still be producing plenty of testosterone. Even though testosterone is a far weaker androgen than DHT, if there is much of it, it is going to be a fine fuel source for the cancer, even if DHT has been greatly reduced. My understanding is that Avodart does an excellent job of shutting down most of DHT produced cancer growth.

Dickiedo, this gets us to your question about when to go back on hormonal blockade therapy. I don't have a good handle on that for patients who are not on finasteride or Avodart during the "off-therapy" period, but I'm not alone. I'm convinced that sound and reliable guidelines for going back on therapy have not yet been established whether the patient was on single, combined or triple therapy and whether or not he was on finasteride or Avodart during the off-therapy period. In "A Primer on Prostate Cancer," Dr. Strum wrote about results in the Strum/Scholz practice where they somewhat arbitrarily used 5 as the trigger for going back on therapy for men who had been on combined LHRH-agonist and antiandrogen therapy without finasteride during the off-therapy period. In order to better triple therapy with finasteride maintenance with combined therapy without maintenance, they decided to cut the trigger point in half, to 2.5, for triple, maintained intermittent therapy. However, Dr. Strum has since said that that threshold was somewhat arbitrary. He and Dr. Scholz have said that they later would pay attention to how fast the PSA was rising and adjust the trigger point based on that. In other words, if the patient's PSA was going up very slowly, they would use a higher trigger point. (That's the inside story, Rhonda.)

On the other hand, another of the triple therapy pioneers, Dr. Robert Leibowitz, was comfortable with PSAs during the off-therapy period going as high as 10, provided the pattern of increase did not look like the tell-tale exponential pattern of growing cancer. Not fully understanding that - wasn't that clear about the exponential pattern in Dr. Leibowitz's articles, I used 10 as the rough threshold for my first cycle. It worked well for me, and I've used it for my second and third cycles too; in fact, I'm now somewhat above 10, even though I'm taking Avodart. I'm confident my PSA would drop rapidly and deeply if I went back on triple blockade, based on my case history. I'm not advocating this for everyone. My oncologist is comfortable with my having a PSA a bit above 10 at this point, based on what he has read and heard.

Dickiedo - Based on what the Strum, Scholz, Lam and McDermed research group has found and published, you might be able to slow your PSA doubling rate by going on Avodart or finasteride at this time. In one of their studies, published in a major journal, men who did that were able to stay off therapy twice as long as men who did not do it. (Drs. Strum and Scholz were two of the co-authors of that study.)

Take care,

Jim :wave:[/COLOR]





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