On the Advanced Prostate Cancer Listserv there was a question raised about the need to use an antiandrogen (bicalutamide/Casodex, flutamide/Eulexin, or nilutamide/Nilandron) along with degarelix, the recently approved LHRH antagonist (a drug that halts the production of testicular androgens). Doctors who are knowledgeable about the use of LHRH antagonists (Zoladex, Lupron, Eligard, Viadur and Firmagon (degarelex) will always prescribe an antiandrogen (other than with degarelex) prior to the administration of the drug. When the LHRH antagonists are first administered the body initially works harder to produce androgens which will cause a PSA flare (PSA in this case is a surrogate marker for an increase of tumor load). The radical increase of tumor load can cause symptoms as bone pain, compression of a nerve root, spinal cord compression, or blockage of one or both urethras. This situation is often painful and always dangerous.

Degarelix works differently than the other LHRH antagonist as it does not cause a PSA flare and does not cause an increase in tumor load. So, the next question is, should degarelix be combined with an antiandrogen?

The merits of combining degarelix with a antiandrogen is not a clear cut issue (CAB or combined androgen blockade). CAB eliminates testicular androgens and it also blocks the androgen receptors. CAB comes with additional potential side effects and so it must be weighed as part of the decision making process.
Several randomized trials comparing LHRH antagonists alone (however not degarelex) vs CAB have demonstrated a survival benefit with CAB. However, in one of the largest trials conducted by the United States Intergroup, more than 1,300 men were randomized to undergo orchiectomy vs orchiectomy plus flutamide (an antiandrogen). There was no significant advantage to CAB in terms of time to disease progression or overall survival.

Some investigators believe that bicalutamide (casodex), which is a more potent agent and may be associated with greater survival when used as part of CAB. Recent meta-analysis suggest a small but incremental benefit of noncyproterone antiandrogens in combination with GnRH agonists in terms of overall survival (15% to 20% relative risk reduction). This finding led the American Society of Clinical Oncology (ASCO) recently to advise an informed discussion of the risks and benefits of CAB.

The fly in the ointment is that many investigators believe that the advantages observed in trials that include an LHRH antagonist exist because of the “flare phenomenon,” which occurs with LHRH antagonists alone and may be lost with a short period of treatment with antiandrogens during the expected flare period. – information from the Cancer Network

Since there is no flare period with degarelix it is possible there is no advantage to CAB. It just more adds more confusion in the prostate cancer world.

Since I know that in the very near future I will need to restart hormone therapy I have been thinking about the merits of which drug to use. Prior to yesterday, I thought that degarelix would be my poison, however after reading about the European study that demonstrated that degarelix might serve as a good 2nd line hormone block (see my post of August 2, 2010 (http://advancedprostatecancer.net/?p=184 ) I am strongly leaning to being more traditional and taking casodex along with Lupron. My question is for how long to continue the casodex. Last round I stayed on it for the entire protocol, now I am not sure that I will.

Joel T Nowak, M.A., M.S.W.