Note: The terms “luteinizing hormone” (LH) and “gonadatropin” (Gn) are variously used by different authorities. Thus, LHRH and GnRH are also interchangeable terms in the medical literature. As far as The “New” Prostate Cancer InfoLink is aware, neither term is considered to be “absolutely correct.” We have chosen to use the terms LH and LHRH throughout this web site as a matter of consistency.
Introduction
The first luteinizing hormone-releasing hormone (LHRH) antagonist (abarelix) was developed in the 1990s and brought to market under the brand name Plenaxis™ in 2003. However, this drug had a number of characteristics that made it unattractive to the medical and the patient community as a treatment for prostate cancer. The most significant of these was a risk for serious and even life-threatening allergic reactions to the drug shortly after its administration. The manufacturer discontinued availability of this drug in 2005. However, considerable information is still accessible through the US Food & Drug Administration’s web site.
Today there are no LHRH antgonists approved for use in the treatment of prostate cancer or any other disorder. However, a “second generation” LHRH antagonist (known as degarelix) is expected to complete phase III clinical trials in late 2008 or early 2009. Depending on the results of those trials, it may become available for the treatment of prostate cancer.
What are LHRH Antagonists, and How Do They Work?
LHRH antagonists are agents that block the activity of human hormone luteinizing hormone-releasing hormone. In other words, they simply stop the LHRH from stimulating production of luteinizing hormone (LH). Therefore there is no luteinizing hormone available to stimulate the production of testosterone.
The great theoretical benefit of LHRH antagonists as compared to LHRH agonists is that there is no “flare reaction” associated with their use. In other words, there is no short-term boost to testosterone production at initiation of LHRH antagonist therapy. This also means that there is no apparent need for the short-term use of nonsteroidal antiandrogen therapy at the initiation of LHRH antagonist therapy.
The Clinical Effectiveness of LHRH Antagonists in Prostate Cancer
With the limited use and subsequent withdrawal of abarelix, we really have almost no useful information about the long-term clinical effectiveness of LHRH antagonist therapy in the management of prostate cancer. Until data becomes available on the clinical effectiveness of degarelix from the Phase III trial program, it is not even wise to speculate on the relative value of this product compared to LHRH agonist therapy.
The Side Effects of LHRH Agonist Therapy
We have already noted that the “first generation” LHRH antagonist, abarelix, was associated with a significant risk for serious allergic reactions. Clearly, degarelix will have to demonstrate that it has overcome this problem if it is to be a product that is widely used in the management of prostate cancer.
We can expect degarelix to be associated with all of the major adverse reactions that are associated with testosterone suppression, potentially including:
- Impotence because the normal testosterone levels have been reduced to castrate levels
- Hot flashes, similar to those which occur in women during menopause
- Gynecomastia or nipple tenderness in which there is mild swelling or at least tenderness of the man’s breasts
- Depression or depression-like symptoms and
- Weight gain
However, the complete range of side effects that may be associated with degarelix will have to await the results of ongoing clinical trials and evaluation of the results of those trials by the manufacturer and global regulatory authorities.
For full information on the possible adverse events associated with any drug, please see the full prescibing information for that specific product.
