 This concurs with the theory that flutamide and nilutamide antagonize AR through the mechanism of “passive antagonism”, as they are of a more modest size then bicalutamide.These drugs may therefore be effective as a second-line therapy for refractory prostate cancer previously treated with bicalutamide.Antagonists of the N-terminal domain (NTD) of the AR have been proposed to overcome the limitations of current antiandrogens regarding mutant ARs, by directly blocking AR function from protein surface, outside of the LBP.