From: "Dr. D. Kossove" <doctordee@telkomsa.net>
To: "lms List"
Subject: The Role of Anti-Aromatase Ihibitors in the Adjuvant Setting  MEDSCAPE CME
Date: Tuesday, November 18, 2003 11:16 AM

ULMS people:  

Exemestane is an irreversible binder to estrogen receptors.
It results in a more androgenic response than letrozole or arimidex.
Wonder if it is worth doing androgen receptors on the tumors? 
Worth reading up on it.  

 Would anyone discussing aromatase inhibitors with their doctors ask about androgen receptor testing, exemestane, and possible influence on estrogen receptor cancers?

Go to MEDSCAPE, register, go to the CME center, and search for this article.  

doreen
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Slide 14. Urine Bone Markers: Overall Baseline-Adjusted AUCs Per Treatment Group
This is a human data slide, a 3-month biomarker study comparing letrozole, placebo, and exemestane in human postmenopausal volunteers. These are important data, but not quite as clean as the rat.

At the bottom are markers of bone formation and at the top are markers of bone resorption, and if you look at it in the postmenopausal placebo group of patients, the bone is changing just a little in 3 months. You don't expect a large difference in metabolism. Likewise, exemestane looks very similar. At this early stage, it's inseparable in a way from the placebo, whereas letrozole has this dramatic bone sucking effect. Bone formation is reduced as well.

I don't want to over-interpret these data, but the ultimate proof is it's like driving a golf ball. You don't have to be far off for the ball to land a long way off the fairway. So if you're doing a 5-year adjuvant therapy, and you have a slight negative effect on bone, it's going to culminate in a problem. If you have a slight positive effect, it's going to culminate in a good.

I predict that, as time unfolds, exemestane will show itself as pretty good in bone in postmenopausal women because of these bone biomarker findings in these animal data. The proof of this will come later.

Not only do we need BMD data to follow this up, we ultimately need clinical fracture data. You can't even judge based on BMD because the correlation between BMD and the risk of clinical fracture isn't directly correlated. The proof will finally be in the clinical fracture rate in these trials at the end.


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