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The combination of enzalutamide, abiraterone acetate, dutasteride, and degarelix is an intensive neoadjuvant androgen deprivation therapy (ADT) regimen investigated in a Phase II clinical trial (NCT01503229) led by Dr. Kenneth Pienta. This regimen, often referred to as 'total androgen blockade,' targets the androgen signaling axis at multiple levels to achieve near-complete inhibition of androgen receptor (AR) activity in men with high-risk localized prostate cancer prior to radical prostatectomy. Enzalutamide acts as a potent AR antagonist; abiraterone acetate inhibits the CYP17 enzyme complex to block extragonadal and intratumoral androgen synthesis; dutasteride inhibits 5-alpha reductase to prevent the conversion of testosterone to the more potent dihydrotestosterone; and degarelix serves as a GnRH antagonist to rapidly suppress testicular testosterone production. Prednisone is typically co-administered to mitigate the mineralocorticoid excess side effects associated with abiraterone.
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