David I. Quinn: Steroids and Prostate Cancer

The Group Room at the 2012 European Society for Medical Oncology (ESMO) Congress in Vienna was made possible, in part, by:

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VIDEO TRANSCRIPT

Selma Schimmel, Founder & CEO, Vital Options International

This is Selma Schimmel for The Group Room at the ESMO 2012 Congress happening now in Vienna where we’re joined by Dr. David Quinn, who is the Medical Director of the USC Norris Cancer Hospitals and Clinics.  He is the Leader of the Developmental Therapeutics Program at the Head of the section of Genitourinary Medical Oncology, and Associate Professor of Medicine in the Division of Cancer Medicine and Blood Diseases at the Keck School of Medicine at The University of Southern California.   I have a question about steroids.   Most people understand that steroids are an anti-inflammatory agent.

David I Quinn, MD:  Medical Director, USC Norris Cancer Hospital, Los Angeles

Yes.               

Selma Schimmel, Founder & CEO, Vital Options International

What role does that have?

David I Quinn, MD:  Medical Director, USC Norris Cancer Hospital, Los Angeles

Good question.  So before we had chemotherapy for castrate-resistant disease, we had steroids which produced a PSA response and an improvement in pain but no improvement in length of life, so no overall survival benefit.  Steroids were sort of part of the first treatment we had when we had nothing, literally.  And so from that perspective what happened was that when we did the first trials of mitoxantrone nowhere compared to steroids, either prednisone or hydrocortisone.  So mitoxantrone was approved as a palliative agent, was superior to steroids alone and then mitoxantrone was compared with two docetaxel regimens which had steroids in them.  And now we’re stuck with the steroids because the registration for docetaxel is with prednisone 10 mg a day.  And the issue then evolved a little bit when abiraterone came around producing significant secondary hyperaldosteronism.  What does that mean?  Well, it blocks the adrenal gland and puts out a hormones up that increase your potassium in your blood pressure.  Now, to block that you can either give a specific complex blocker of one of the mechanisms in the adrenal or you can give prednisone or another steroid which will stop most people becoming hypertensive, getting high blood pressure or their potassium going up.  But we don’t know how much an individual patient needs and most patients probably don’t need very much at all.                   

Selma Schimmel, Founder & CEO, Vital Options International

And most patients don’t like taking steroids.

David I Quinn, MD:  Medical Director, USC Norris Cancer Hospital, Los Angeles

 They don’t like taking steroids because they make them cushingoid, fat; they put their blood sugar up and also increase their blood pressure, etc.  And so from that perspective we’ve got health consequences from these things.  They also increase osteoporosis.  So from that perspective looking at the steroids is important. 

Johann de Bono’s team at Marsden has done very interesting work with this and looked at whether we should be using different steroids, dexamethasone which has less peripheral effects, more central effects rather than prednisone and probably the answer is that would be a better steroid given at an equivalent dose.  And then the other question we’re asking, particularly related to some of these chemotherapies and abiraterone is, do you really need the steroids? Does every person need to be on a steroid at all?  And I think in practice what a lot of the oncologists are trying to do to is, say, abiraterone, which is a new drug, is to actually reduce the dose of steroids whether it be prednisone or dexamethasone in the patient so that you are watching them carefully to make sure you don’t lose control of their disease.  And also just try to wean down the steroids just a little bit.  What we saw yesterday was a really interesting presentation on a new drug that doesn’t require steroids, Medivation 3100 or enzalutamide.  And this class of androgen receptor antagonists or super androgen receptor antagonists that have a greater effect than drugs like bicalutamide (Casodex)or flutamide do not require steroids.  They don’t have any sort of secondary effect that would require it.  But in the AFFIRM study, which was a study for patients who’d had prior docetaxel chemotherapy, there was a placebo arm and a Medivation 3100 or enzalutamide arm and patients were permitted to take steroid therapy as part of supportive care but also allowed to have some other things as well like radiation therapy and support for their bone and what have you.  Well, interestingly, if they took steroids, their overall survival in both groups was significantly worse.  And so, this was a late-stage study; these people had a lot of therapy, so enzalutamide produced a major overall survival advantage. 

So I think steroids can be a little confusing.  What we’re talking about in this instance is daily steroids given as part of a therapy and I think we’re going to be asking some questions about that particularly across prostate cancer.   We’ve already addressed this 20 years ago in breast cancer and the studies adding prednisone were negative to standard chemotherapy.  And, clearly what I’m talking about is the daily administration of, say, prednisone, and dexamethasone.  I’m not talking about the pre-chemo, the day of chemo and day after chemo steroid treatment.  Usually dexamethasone we give for docetaxel (Taxotere) or paclitaxel (Taxol) to suppress allergic reactions.  They’re still important and they probably don’t have an adverse effect.  In fact, they are necessary for a lot of patients; their allergic reaction rate goes really high if we don’t give them.               

Selma Schimmel, Founder & CEO, Vital Options International

Dr. David Quinn, Medical Director of the USC Norris Cancer Hospital and Clinics, Leader of the Developmental Therapeutics Program for the USC Norris Cancer Hospitals and Clinics, Head of the section of the Genitourinary Medical Oncology Unit, and Associate Professor of Medicine in the Division of Cancer Medicine and Blood Diseases at the Keck School of Medicine at The University of Southern California.

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