I don’t understand why if I have hormone resistant advanced prostate cancer why the new drugs, Zytiga and Xtandi work. These drugs are still hormone therapies, is my prostate cancer hormone resistant? I recently received an email asking me this question and I thought it might be a question many people have, so I am going to answer this on the blog.
First, I want to be clear, yes Zytiga and Xtandi are both hormonal therapies that do work for many men when their cancer has been classified as hormone resistant.
The failure of Lupron etc. and Casodex does not mean that our cancer no longer is dependent upon testosterone. What it really means is that our cancer now has adapted itself and become more sensitive to lower levels of testosterone and is able to find alternative sources of testosterone. Simply put, the Lupron and Casodex are no longer powerful enough to do the job.
This change is the result of three different mechanisms. We have now found out that prostate cancer cells themselves are capable of making their own testosterone, making them independent of outside sources; the cancer cells often are able to modify their androgen receptor so that Casodex encourages the cancer growth by treating the drug as if it were testosterone. (This is why in many men stopping Casodex will initiate a positive response) and the androgen receptor becomes more sensitive so that it needs much lower levels of testosterone to continue growing.
To be accurate it is quite uncommon for prostate cancer to become androgen independent. This understanding of the progression of prostate has led us to the new forms of hormone therapy using Zytiga and Xtandi
Zytiga (given along with prednisone) was the first FDA-approved drug to respond to this understanding. Zytiga ‘s mechanism of operation is simple, it is much more efficient at blocking testosterone production then Lupron. Its most important difference is that it blocks testosterone production throughout the body; including the adrenal glands and the cancer cell itself. Zytiga is more efficient at lowering the levels of testosterone production in the entire body (not just from the testis).
The other new hormone therapy drug is known as Xtandi and it has a different mechanism of action from Zytiga and the other hormone therapy drugs. Xtandi has been called a “Super Casodex” because like Casodex, it binds to the androgen receptor, however Xtandi is five fold better at competing with testosterone for the androgen receptor than is Casodex. Xtandi uses different pathways that are used by Lupron and Casodex and is able to work even while Lupron and Casodex have failed.
The bottom line is that it is a misnomer to call prostate cancer that has begun to progress in the face of Lupron (etc.) and Casodex hormone resistant. In fact prostate cancer at this stage is still dependent on the androgens, but the cancer has actually developed additional pathways around these first stage treatments so that it can continue to progress. Zytiga and Xtandi respond to these new pathways, but they too only respond for a limited time as this cancer is able to develop even more new pathways.
Joel T. Nowak, M.A., M.S.W.
Thank you for your explanation in a way I find easy to understand. I just started Lupron and I am weighing whether I Should be on Xtandi instead of lupin or combination or the two. I see i Europe that XTandi is becoming the firs option in cases like mine over Lupron
I wonder since I’m on Lupron already would a full does or maybe better a half a dose of Xtandi help or hurt in lowering my PSA and killing as many cancer cells as possible. My goal is get my PSA ( and the cancer) to as low a level as possible and then have a combination of Proton then followed by photon therapy to try in combination with the Homone treatment to try for a remission or at least to restart the clock with my prostate cancer and maybe another 7 year window.
Loma Linda’s proton centre says they have had good results with this combination approach and I want to give it a shot. Any input and incite would be greatly appreciated. My biopsy was a 9 Gleason with 9 out of 13 positive needles. My PSA was 50 before I started the Lupron 30 days ago.
Not good numbers I know but I still want to have hope. Hope that is possible to extend my life more than just a few years while keeping a decent quality of life. Im 72 and otherwise very healthy.
Ive read a few online articles that seem to indicate multi pronged approach can be very helpful.
The new vaccination with PROSTVAC Sems like the future, but when..
Rick, Refer to my response to you under the post titled: Analyzing Time to Developing Castration-Resistant Prostate Cancer and Overall Survival after Initiating Androgen Deprivation Therapy (ADT). I believe that I responded to most of your questions in that reply.
I do agree that you have a significant level of aggressive prostate cancer. I also agree that you should be positive. I see no reason that you can not continue to live a long life with a good quality of life. – Joel