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.
Joel, most interesting article on Degarelix being added to normal therapy…BUT…I see your second round will not include this and you will keep with traditional Casodex with Lupron
Question: Am I assuming you feel more comfortable not using DEGARELIX.???
Thanks and have a great day.
Lee,
My thinking is to hold off using Degarelix as a first line hormone treatment and when Lupron and Casodex stop working I first will just stop Casodex, then my next shot will be to try Degarelix. Of course, then on to Keto etc. My thinking is that Degarelix works using a totally different pathway, so maybe it will still snuff out the testosterone even when Lupron fails. It is my personal experiment, no evidence that it will work, but if not then I quickly move on to Keto. — Joel
Stage 4 PCA. Gone through chemo radiation. Been on casodex and trelstar for 15 months. Testosterone levels >20 psa 2.0
Got a shot of degarelix, 7 days later testosterone 600 psa rising 14.5. Went back to trelstar within 14 days testosterone dropped to >20 and psa still rising 24.5 Had tomotherapy – claened up my pca in prostate and right pelvic area – was crusing – then the spike with degarelix – 3 lesions in back and rib cage. Question – can you mix these drugs trelstar, casodex and degarelix (agonist/anagonist) ????? HELP-Jay
It looks as though you are now castrate resistant. Look into Provenge now and then you should follow up with ketoconazol. – Joel
Joel, funny thing. I’ve been having low test/psa for over a year, in 2/11 the nurse (for some reason, Urologist didn’t know) gave me Degarelix (Been on Trelstar/casodex) test/psa shot up real high test 600 psa 16. Told him, got shot of Trelstar in 5/11 14 days later everything down to normal. Meanwhile then want me to start chem/castration. Now every down they said don’t need to to castrated or chemo. Any thoughts. Did love the info on ketoconazol will talk to Ongologist Tuesday 7/5. Thank you Jay
Jay, That sounds pretty weird, wow.
I wonder if the nurse gave you the degarelix properly. There are a number of places that she could have made a mistake. 1- She would have had to mixed the degarelix right before she gave you the injection, perhaps ahe did not mix it correctly? 2- The first dose of degarelix is called a loading dose, it requires two different injections, did she give you the loading dose or just one injection? 3- Giving degarelix requires the injection to be done in a very specific manner, it requires the proper angel of the needle and positioning the medication properly in the belly fat and 3- The needle needs to be completed emptied prior to its being withdrawn, sometimes this is not done correctly. – Joel
Joel
Thank you for the information – only recieved one injection – plus I understand a 28 day booster is also required – I didn’t recieve anything till my May 2011 (3 month) shot came up and did recieve Trelstar which immediatetly reduced testosterone
to <20 PSA still rising 24 but Oncologist pretty confident that will drop soon. I have been having alot of pulled muscle,
ligment strains etc., I am fairly active with golf – and working out – I was told chemo reduces the strength of the muscle to bone for awhile – any imput – Thanks Jay
Jay,
Degarelix is only a one month injection and must be “renewed” every 28 days. Trelstar comes in different dosages so the frequency of “boosters” varies depending upon the dose received. – Joel
Joel,
My husband had robotic prostatectomy done in Feb 2012. He had cancer in one lymph node. Bone scan negative. Pelvic 1.5 Tesla MRI showed no evidence of anything left behind. Pre-Surgery PSA 19. Post surgery PSA 25. Started on Trelastar. PSA 12 a month later. Trelstar injection dosage increased. 3 months later PSA 25. Started on Casodex. Pre- Surgery weight 238. Today he weighs 220 lbs. His urologist suggest he see a medical oncologist which will be tomorrow. I ran across the drug degarelix and plan to ask his medical oncologist if he should start taking it since it brings down the PSA without flaring within 3 days. Does trelstar cause muscle wasting ? It did cause hyperglycemia and he is taking Metformin now. Thanks Vee
Vee,
It is good that he is now seeing a medical oncologist, but make sure the oncologist treats a lot of men with prostate cancer. Proper treatment of advanced prostate cancer takes experience and flexibility. He should have been put on Casodex prior to the Trelastar, but that is now water under the bridge. I do think that moving from Trelastar to Firmagon is a good plan, he did not respond to the Trelaster. The goal of hormone therapy is to bring his testosterone levels to a castrate level, often the failure to drop the PSA as in your husband’s case can be attributed to his not becoming castrate. So, the question is has his testosterone level been looked at? If not, have it done now. In answer to your question about muscle wasting, the answer is yes it often does. It is vial that he have a regular exercise schedule that includes both aerobic and weight bearing exercise. Perhaps he should consider using a trainer to help set up a program that would be safe for him.
Joel
IS IT DANGEROUS TO BE OVERDOSED WITH DEGARALIX?
JUST WONDERING AS MY DAD WAS GIVEN THE SAME DOSAGE AS THE FIRST INITIAL FOR 4 MONTHS AND IT ONLY STOPPED WHEN I QUERIED IT
THEY THEN ASKED FOR BLOOD TESTS TO CHECK HIS LIVER EVEN THOUGH THEY SAID THAT THE EXTRA DOSES WON’T DO HIM ANY HARM.
I WAS TOLD HIS BLOOD TESTS CAME BACK FINE,NO WORRIES WHATSOEVER BUT WHEN I CALLED OUR DR TO SEE ABOUT AN ANTIBIOTIC SHE TOLD ME THAT MY DAD WASN’T ALLOWED THEM AS HE’S GOT BAD LIVER DAMAGE AND WHEN I QUERIED THE REASON FOR THAT SHE SAID BECAUSE OF MY DAD’S BAD ALCOHOL PROBLEM BUT MY DAD DOESN’T DRINK ALCOHOL AT ALL AND THE LAST TIME HE HAD A DRINK WAS AT XMAS 33 YEARS AGO.
DO YOU THINK THAT THIS IS A COVER UP?