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This combination therapy consists of **apalutamide**, a second-generation androgen receptor antagonist, and **leuprolide**, a gonadotropin-releasing hormone (GnRH) agonist. Apalutamide works by binding directly to the ligand-binding domain of the androgen receptor, inhibiting nuclear translocation and DNA binding, thereby preventing testosterone from promoting prostate cancer cell growth. Leuprolide acts by initially stimulating but subsequently desensitizing GnRH receptors in the pituitary gland, leading to a profound reduction in testicular testosterone production (chemical castration). This specific regimen utilizes an intermittent hormone therapy (IHT) approach, where leuprolide is administered in cycles to allow for testosterone recovery periods, aimed at improving quality of life and delaying the development of castration resistance. The combination is currently being evaluated by The University of Texas Health Science Center at Houston for the treatment of men with biochemically recurrent prostate cancer.
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