Which ADT Is Smarter for the Heart?

Gerald Chodak, MD


June 20, 2016

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Hello. I'm Dr Gerald Chodak for Medscape. Today I want to talk about the use of a luteinizing hormone-releasing hormone (LHRH) agonist or antagonist for the treatment of men with metastatic or advanced prostate cancer. A few years ago, the US Food and Drug Administration issued a warning about the possible cardiovascular (CV) risk associated with the use of these drugs—at least for the agonists.[1]

Recently, Rosario and colleagues[2] were part of a roundtable discussion that was cited in the Prostate Cancer InfoLink website. They talked about relative risks of the antagonist and how to counsel men who are candidates for therapy. They did an analysis and found that for men who received androgen deprivation therapy (ADT) with an antagonist vs an agonist, there seemed to be a lower risk for CV events in men who had a history of cardiovascular disease (CVD). That same finding was not discovered in men who had no risk for CVD. The concern may really be for treating men with a history of CVD as a preexisting condition.

Obviously there are some disadvantages for using the antagonist, namely that local side effects from the injections are significantly higher compared with the agonists. The antagonist also causes a more immediate rapid decline in testosterone and a more rapid decline in prostate-specific antigen—both factors that may have some association with long-term impact. So far there are no randomized data suggesting or proving that the use of an antagonist improves survival compared with the use of agonists. The other thing that must be considered is that men in the antagonist randomized trials had the use of the agonist leuprolide, which for several reasons may not be as good as, say, triptorelin, which was not included in those trials.

Current management of men with newly diagnosed metastatic disease consists of a combination of an LHRH drug with docetaxel because this has been shown to significantly improve survival.[3] However, there's no evidence of a difference in CV outcomes or risks; the data were not presented and divided according to the use of ADT therapy.

Where do we stand today? We still have no proof that the antagonist offers better survival, but at least for the men that have a history of CVD, there may be a lower risk of having a CV event while they are receiving ADT therapy. If the situation had been reversed and the antagonist had been developed before the agonist, these discussions probably wouldn't exist. There's no question that there are clear advantages to the antagonist, and hopefully someday it will be easier to administer with less discomfort.

For now, a good discussion should occur with all men who are going on ADT therapy, and those with a history of CVD should be made aware that there might be a lower risk for an event occurring from receiving the antagonist compared with the agonist. I look forward to your comments. Thank you.


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