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    Old 12-07-2009, 10:41 AM   #1
    positional
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    Hormonal therapy

    Hello,

    My brother was diagnosed in April this year with the advanced PC. PSA was 67 and Gleason score 8-10.

    Since then he was put on Cosadex, Zoladex and Zometa (triple blockade?).
    He got metastasis in his bones. PSA dropped significantly to 4.

    But, at some point, PSA started rising and his doctor decided to cancel Casodex. Since then, PSA keeps dropping every week (34, 29, 24 and now 15). His pain (mostly from bones) still persists, but, after he took Zometa again couple of days ago, he feels better.

    Is there anyone who experienced a similar PSA dropping trend?

    Also, what the next step should be in terms of what drugs or combination of them?

    Thanks in advance.

    Mark

     
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    Old 12-08-2009, 10:15 AM   #2
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    Re: Hormonal therapy

    Hello Mark. Sorry to hear about your brother's situation. Jim or others who are more knowledgeable than I am will probably respond with some thoughts, but I will give you a few to begin with. First, Casodex, Zoladez and Zometa is a common combination for advanced p ca, but it is not what people typically refer to as "tripple blockade." Zoladex inhibits the production of testicular androgen (testosterone). Casodex inhibits testosterone produced by the adrenal glands. So maybe that is a "double blockade." The zometa is different -- it does not block testosterone production, but instead helps strengthen bones (and may reduce bone mets). It is not unusual for psa to drop -- at least for some time -- after going off Casodex. Some oncologists will add a third "blockade" to the Zoladex (or other LHRH agonist) and Casodex, which blocks the conversion of testosterone to DHT (DHT feeds the cancer, so it is good to block the production of DHT). These drugs, referred to as 5-alpha-reductase inhibitors, include finasteride and dutasteride. You could ask about that.

    There are a number of other treatments that are used, in various combinations, for advanced prostate cancer cases, including -- as just a few examples -- ketoconazole (you will sometimes see LDK or HDK, for low dose keto and high dose keto), taxotere (and some other chemotherapies, but that is the most common), estradiol (and other estrogens), DES, leukine (which you may also see referred to as GM-CSF, granulocyte macrophage colony stimulating factor), thalidomide, and some new treatments, including something called "Provenge" which is not yet on the market, but is making progress after a long delay at FDA. So there are lots of options.

    The best suggestion I can make for your brother is this: Make sure he is treated by (or at least consults with) an oncologist who is a true expert in prostate cancer. It is a complicated field to keep up to date with, and it is very hard for a generalist oncologist (even a really good one) to keep fully up to date. But there are some oncologists who spend most or all of their time on prostate cancer cases, and in my view that is who you want to consult with. If you tell us where your brother is located, we might be able to suggest some nearby experts.

    Best wishes,

    Medved

    Last edited by medved; 12-08-2009 at 10:15 AM. Reason: correct typo

     
    Old 12-09-2009, 07:24 PM   #3
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    Re: Hormonal therapy

    Hi Mark,

    Welcome to the board!

    Medved did a fine job going over the territory, so I'll just join his tag team.

    I strongly recommend that your brother get a book by Dr. Charles "Snuffy" Myers, MD, entitled "Beating Prostate Cancer: Hormonal Therapy & Diet." It starts off with a strong belt of optimism, which your brother probably needs, and it gives details and examples of the options that Medved mentioned. I'll insert a few comments in your post below, in green.

    Quote:
    Originally Posted by positional View Post
    Hello,

    My brother was diagnosed in April this year with the advanced PC. PSA was 67 and Gleason score 8-10.

    As you probably know, your brother is facing a challenging case. I am too, in fact my baseline PSA ten years ago was even higher (113.6), but I had a big advantage in that my Gleason Score was a 4+3=7. That may not sound much better than the 8-10 (do you know which?), but it is.

    Since then he was put on Cosadex, Zoladex and Zometa (triple blockade?).
    He got metastasis in his bones. PSA dropped significantly to 4.

    It's likely the removal of Casodex made the difference, though it's my impression that it's not usual for the cancer to mutate so quickly so that it can use the Casodex as a fuel.

    But, at some point, PSA started rising and his doctor decided to cancel Casodex. Since then, PSA keeps dropping every week (34, 29, 24 and now 15).

    That's a good trend, but the PSA needs to drop a lot lower to really knock back the cancer. He probably is still producing too much dihydrotestosterone (DHT), and that is a far more potent fuel for the cancer than testosterone. He probably needs to be on Avodart or finasteride, which will block almost all or most of the conversion of testosterone to DHT. He should probably be tested for both testosterone and DHT, which should be standard practice for men on hormonal blockade, but often is not done.

    His pain (mostly from bones) still persists, but, after he took Zometa again couple of days ago, he feels better.

    In addition to helping with bone density, Zometa often helps slow down, stabilize, or even reduce the growth of bone mets, and that would be consistent with your brother's feeling better.

    Is there anyone who experienced a similar PSA dropping trend?

    Twice my PSA has dropped all the way down to <0.01, at which point I took a vacation from the heavy duty drugs, as recommended by expert doctors. This third round on triple blockade, my PSA has dropped from 9.53 in September 2008 to 0.05 on October 28, my last test. I'm trying to reach <0.01 again. The experts in hormonal therapy whom I follow believe the patient needs to get the PSA down to <0.05, or ideally to <0.01. If the PSA stops moving toward <0.05, they usually will switch some elements of the therapy.

    Most men on hormonal blockade will have a much sharper plunge in PSA than your brother or I have had, but we have more challenging cases than those men. It's like the singing pig: he may not sing well, but it's a wonder that he sings at all!


    Also, what the next step should be in terms of what drugs or combination of them?

    I'll echo Medved's suggestion of ketoconazole (with hydrocortisone) as a substitute for the Casodex. It's a stronger drug, but there are some management challenges as it interacts with quite a few other drugs that your brother might be on. It's really good to have a doctor experienced in using ketoconazole successfully with reasonable side effects. Some of the other approaches Medved mentioned could also work well.

    Thanks in advance.

    Mark
    Take care,

    Jim

     
    Old 12-12-2009, 05:52 PM   #4
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    Re: Hormonal therapy

    Medved and Jim,

    Thanks for the valuable input.

    My brother lives in Moscow, Russia. Since my last post, his PSA dropped even more to 5.86. His doctor (they have a huge cancer center in Moscow) is going to put an isotope of strontium (if I translated correctly) in the vein to reduce the bones metastasis pain. That's going to happen next wekk. I wonder if this is (radiation) a technique used here in US as well.

    Also, as a next step, doctor considers either orchiectomy or ketoconazole. Ketoconazole is not available in Russia. Can I buy it in US and send it overseas or I need a prescription for that?

    I've read about Provenge, but it's not yet available.

    Thanks again.

    Mark

     
    Old 12-13-2009, 05:20 PM   #5
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    Re: Hormonal therapy

    Hi again Mark,

    I'll add some thoughts in green in an excerpt of your post immediately prior to this post.


    Quote:
    Originally Posted by positional View Post
    Medved and Jim,

    Thanks for the valuable input.

    You're welcome. I hope we can continue to help.

    My brother lives in Moscow, Russia. Since my last post, his PSA dropped even more to 5.86.

    That's a good looking trend downward.

    His doctor (they have a huge cancer center in Moscow) is going to put an isotope of strontium (if I translated correctly) in the vein to reduce the bones metastasis pain. That's going to happen next wekk. I wonder if this is (radiation) a technique used here in US as well.

    Yes, that is a standard approach for bone pain, and it is often quite effective. I'm just wondering though if the pain will continue to ease and even go away without strontium as the hormonal blockade and Zometa continue to do their work. My impression is that that often happens. My understanding as a layman paying attention to expert doctors is that Zometa is most effective against established bone mets when it is given every three to four weeks. However, as time goes by, the risk of osteonecrosis of the jaw ("ONJ", basically, disintegration of part of the jaw bone) becomes more likely, though still not common. Zometa delivered as far apart as every three months minimized ONJ in one practice (Scholz/Lam, Marina del Rey, CA). I can visualize where the doctors would try to balance the dosing and pain relief needed, perhaps in conjunction with strontium. Did the doctor say he would give the strontium after seeing the latest PSA result of 5.86? I'm thinking that after seeing that fine result and steep downward trend, he might decide to hold off and see if Zometa and hormonal blockade can sufficiently push back the bone mets and reduce pain. It's been a long time since I learned about strontium for relieving pain from bone mets, but my lingering impression is that it is pretty well tolerated by patients. However, it does do some damage to the bone marrow, as I recall, reducing its capacity to do its jobs. That means that strontium is not an entirely free ride for the patient. There are lots of points to consider and balance here.

    Also, as a next step, doctor considers either orchiectomy or ketoconazole.

    I'm a little puzzled here, as Zoladex does the same job as orchiectomy, so there would not be a clear gain medically as I see it. However, the orchiectomy would be permanent and would eliminate the need for any more Zoladex doses.

    Ketoconazole is not available in Russia. Can I buy it in US and send it overseas or I need a prescription for that?

    It's a prescription drug. I'm not sure if a Russion doctor could write a prescription that would be honored here, but it would be worth looking into. Of course, your brother could also travel once to the US for a consultation and get a prescription that could be refilled indefinitely (I think - not sure about that).

    I've read about Provenge, but it's not yet available.

    Even when it becomes available, the FDA approval will not cover men like your brother who are still able to respond to hormonal therapy. However, in the US, once approved by the FDA for one use, it can be used under "off-label" rules for other purposes. That might make it available for men like your brother. I'm not sure how insurance will cover off-label use in the US. It's going to be expensive - probably tens of thousands of dollars for a three dose course of the drug.

    Thanks again.

    Mark
    Take care,

    Jim

     
    Old 12-14-2009, 10:57 AM   #6
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    Re: Hormonal therapy

    Hi Jim,

    As always, thanks for your thoughts.

    The problem we and my brother's doctor are trying to resolve is, despite the fact that PSA keeps dropping and Zometa is taken every four weeks, bone metastasis pain gets stronger. That's why the strontium was introduced to the mix. The doctor's prediction is, after strontium is in, the first 5 days it will be worse before it gets better later on.

    The pain, for obvious reason, has to be addressed first.

    I will keep you updated.

    Mark

     
    Old 12-14-2009, 07:18 PM   #7
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    Re: Hormonal therapy

    Hi Mark,

    I thought it was probably the situation you described in the previous post, #6, but I thought it was best to mention alternatives to be sure.

    Take care,

    Jim

     
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