How does prostate cancer work? With Andrew Schorr as host, Dr. Russell Szmulewitz of the University of Chicago Medical Center gives a short description of the endocrinology of prostate cancer and provides an overview of hormonal therapies. Listen as Dr. Szmulewitz examines the changing treatment paradigm including risks and benefits.
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Transcript
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Andrew Schorr:
Dr. Szmulewitz, so my understanding is, typically, the fuel for prostate cancer are hormones, right? And that’s where hormonal therapy comes in.
Dr. Szmulewitz:
Yes. So we’ve known for 70 years now that prostate cancer, in many ways, is dependent on the male hormone testosterone and other male androgens that are made by the body and even the tumor itself to sort of fuel the disease. And so for advanced disease, hormone therapy, therapy that is designed to either reduce the levels of hormones in the body or block the receptor that uses those hormones is, in many ways, a centerpiece of the therapy that we get.
Andrew Schorr:
Okay. So we have a bunch of them on the screen there, different names. Some have been around for many years. I know leuprolide acetate (Lupron), maybe some of the others have been used for generations. I know my father received that. But there are many others now. And then newer drugs, anti-androgens, there are some newer drugs as well. So tell us where we are in trying to fight the fuel for the prostate cancer, Dr. Szmulewitz.
Dr. Szmulewitz:
Okay. So it’s a great question. And I think that we have to understand a little bit about endocrinology, how hormones are produced and how they work. The primary male hormone in the body is testosterone, and it is probably 95 percent of the male hormone in a healthy adult male. And it’s made by the testicles. So the centerpiece of hormone therapy, the biggest bang for the buck, if you will, is to get rid of testosterone.
And so we do that primarily by one of two ways. And one is surgical castration, removing the testicles. And that’s, obviously, been around for generations. And the other way is through chemical blockade of the production of testosterone. And that is done with GNRH analogues or LHRH antagonists. And on the slide that you have in front of you, that’s the Leuprolide, degarelix (Firmagon), triptorelin (Trelstar), Goserelin (Zoladex). Those are different brand names of this class of medication. And they all, essentially do the same thing is they get rid of testosterone production or stop the male hormone being produced in the body.
What we have now learned is that there are other hormones in the body. And prostate cancer, especially as it progresses, those other hormones can be just as important to either block production or to block their utilization within the cancer cell.
And I think that what we’re trying to figure out is at what point should those medications like enzalutamide, which is an anti-androgen or blocker of androgens, or the synthesis inhibitor, abiraterone, at what point should they be used? Because, as you mentioned earlier, the more we do therapeutically, the more potential side effects there are. And there are side effects with all of these therapies. So right now, we understand that one of the ways that cancer adapts to the initial lowering of testosterone is by one, making more receptors, more grabbers of the hormone. And then another is by even making its own hormone.
So the medicine, enzalutamide, which is a very potent, effective blocker of hormone, and the medicine abiraterone acetate, a very effective blocker of the production, are used to counteract some of this adaptation over time.
I know the discussion that’s been going on in your field for a while as you’ve had these new agents come online as well on top of the older ones you’ve had is what drug to use when or what drugs to use in combination. You talked about, for instance, with advanced prostate cancer; you were talking about maybe now surgery, radiation, hormonal therapy, and boom, boom, boom, boom. What about with these drugs?
Dr. Szmulewitz:
So I think that there is going to be a shift of utilization of these drugs from a more advanced and hormonally, castration refractory setting. So in other words, as prostate cancer progresses, initially, we block testosterone production.
And we call that castration either medically or surgically. And castration resistance is where many of these medicines are now used. But I think that, over the next five years, we will be moving these medicines earlier and earlier in the treatment paradigm to sort of hit the cancer hard. And I think we have studies open, and there are many studies open worldwide that are now adding the abiraterone and the enzalutamide to the initial hormonal manipulation to try to choke off the tumor to the most effective wave we can as early as we can. It’s not quite standard yet.
But I would encourage patients that are in the position where they’re having to make these initial treatment decisions to seek out clinical trials that may be asking this very fundamental question of what should we add and how hard should we hit the tumor, because there’s obviously a risk benefit, a side effect versus potential benefit, that we really need to answer.
Andrew Schorr:
Let me just ask you about that. As a leukemia patient, I was in a clinical trial with three drugs used together. And the way my doctor described it to me is we’re trying to hit the cancer in the jaw and in the stomach and cut it off at the knees so that it almost didn’t have an escape route. Is that the idea? Because cancer is wily.
Dr. Szmulewitz:
Yes. So cancer is wily, and I think that definitely is the idea that to use many of these things in combination. For example, the earliest would be before surgery or right after surgery. In other words, we would anticipate that if there is microscopic disease at that time, maybe the most potent time that we can affect cure rates is really by hitting around that time. And so we’ve just completed a national study that’s asking should we give chemotherapy right before surgery with hormone therapy and then surgery?
And there are studies that are being designed and are going to start soon about asking for the highest risk patients. Should we add a bunch of these things right after surgery? And so I agree that surgery and/or radiation and chemotherapy, in certain instances, and most potent hormone therapy, those are the studies that we’re doing now. And that’s, I believe, where we’re going to be in the near future.
Published By :
Patient Power
Date :
Jun 16, 2016
