Are LHRH antagonists more appropriate for some patients than LHRH agonists?

A new paper from a panel of experts in the UK has suggested that the use of LHRH antagonists (e.g., degarelix) may be more appropriate than the use of LHRH agonists (e.g., leuprolide acetate of goserelin acetate) in some prostate cancer patients.

This paper by Rosario et al. is apparently based on a round-table discussion focused on whether LHRH antagonists might come with less risk for prostate cancer patients with concomitant cardiovascular disorders than the LHRH agonists. The entire paper is available on line, so we shall leave individuals to make up their own minds about this issue.

In the paper’s conclusion, the authors make the well-established point that LHRH antagonists provide similar levels of testosterone suppression to the LHRH agonists, …

but have the major advantage of more rapid suppression of testosterone, …, with consequent rapid decreases in PSA, LH and FSH levels.

They go on to add that

Antagonist-based testosterone suppression is also more predictably sustained in the longer term, with less breakthrough than seen with agonists, and may offer improved disease control, compared with [LHRH] agonists.

and that

Antagonists are also associated with a reduced risk of [cardiovascular] events in men with pre-existing [cardiovacular disease], compared with agonists. Mechanisms by which the different CVD risks of agonists and antagonists may occur are still being elucidated, but it seems increasingly likely that [LHRH] agonists stimulate T cell-mediated pro-inflammatory responses, leading to destabilization of atherosclerotic plaques.

Of course it is also generally true that injections of LHRH antagonists into the abdomen seems to be more painful for a high percentage of patients — most particularly for the first such injection, which requires a double dose of the LHRH antagonist degarelix, and so this is also a factor that needs to be considered.

3 Responses

  1. I won’t pretend to say I understood all I read in this paper, but it appeared to me that other than initial injection site reaction degarelix was at the least equal to but typically substantially superior to leuprolide, especially among cardiac patients, a very common comorbidity factor among those elderly men most likely to receive ADT after their primary prostate cancer treatment. If/when I need to consider ADT, degarelix will certainly be high up on my list of possible treatments.

  2. From Erdkamp F, et al. GnRH agonists and antagonists in prostate cancer. Generics Biosimilars Init J. 2014;3(3):133-42.

    “The GnRH antagonists, degarelix and abarelix, show considerably lower scores than the GnRH agonists. Based on current data, these drugs should not be considered as first-line therapy for the treatment of prostate cancer. Their acquisition cost is also higher than those of (the already expensive) GnRH agonists. The 2013 guideline for the treatment of prostate carcinoma of the European Association of Urology assigned a limited place to GnRH antagonists: ‘Overall, this new family of agents seems appealing, but their advantages over GnRH agonists are far from proven. The use of GnRH antagonists is limited by a monthly formulation. Suppression of the initial flare-up with monotherapy is only clinically relevant in a few, symptomatic, metastatic patients’.”

  3. One very well known medical oncologist with a large practice dedicated to prostate cancer patients is a big fan of degarelix. Among other points, he believes that the rapid suppression of testosterone gives the cancer less opportunity to mutate.

    He finds that attention to proper administration of degarelix (duration of injection, use of ice, etc.) sharply reduces injection pain.

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