First generation Nonsteroidal antiandrogen agents

Includes flutamide, nilutamide bicalutamide and enzalutamide.

The first nonsteroidal flutamide, nilutamide bicalutamide agents were less effective than castration in cases of metastatic castration resistant prostate cancer.

First generation non-steroidal antiandrogen’s have partial, androgen agonist activity and inhibit, androgen receptor translocationto the nucleus.

First generation antiandrogen had weaknesses which included a variety of resistant mechanisms, including AR amplification, point mutations, and AR splice variants.

In the presence of excess antigens, these medications switched to agonist behavior, further exacerbating, antiandrogen resistance.