The Synergy between Xtandi and Zytiga with ADT – Is it Important to Continue Taking ADT Along with Xtandi and Zytiga?

This Blog Post has been modified from its original based on comments we received from one of our reader, PaulC.  Thank you Paul for pointing out our error. 


When men with advanced prostate cancer first become castrate resistant (their prostate cancer continues to grow as evidenced by an increasing PSA and or by disease progression on scans), they usually add either abiraterone acetate (Zytiga) or enzalutamide (Xtandi) to their hormone therapy treatment (ADT).  These second-line drugs, Zytiga and Xtandi, are usually not used in place of the ADT, but along with the ADT therapy.  

Why are Zytiga and Xtandi added to ADT and not substituted for ADT?

ADT is designed to stop the production of the testicular androgens which account for a large portion of all the androgen production in the male body.  However, additional androgen production continues from the adrenal glands as well as from the prostate cancer cells when a man is on first-line ADT!  Firstline ADT does not stop the androgen production from the adrenal glands or from the cancer cells. Resulting from the development of mutations in the cancer cells, the cancer can eventually support itself just on the androgens created by the adrenals and the cancer cells themselves despite a man being technically castrate.  

By adding Zytiga or Xtandi to the ADT protocol when a man becomes castrate resistant, the prostate cancer will usually respond positively because it is then denied both the testicular and the adrenal androgens.  

Most doctors believe that stopping first-line ADT when adding Zytiga or Xtandi will allow some testicular androgens to be again manufactured and then support the growth of the prostate cancer.  They believe that using both first-line ADT and one of the second-line treatments like Zytiga or Xtandi provides a more complete blockade in the same way that using a Lupron like drug along with Casodex (ADT2) or a 5-reductase inhibitor like Dutasteride (ADT3) does for first-line hormone therapy. 


This premise has been called into question in some individual cases that Cancer ABCs has come to know.  PaulC who has shared his experience (see comments attached to this revised blog post) as well as another man’s experiences using just Erleada raises the question about the efficacy and the need to continue first-line ADT when a man progresses and moves onto second-line treatment.  


Perhaps the assumption that first-line ADT needs to be continued along with second-line treatment needs to be evaluated in a more formal clinical trial setting. 




By Joel T Nowak, MA, MSW