ketoconazole + dexamethasone

Ketoconazole + dexamethasone is a combination therapy investigated for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Ketoconazole acts as a non-steroidal inhibitor of the enzyme CYP17A1 (17α-hydroxylase/17,20-lyase), which is essential for the biosynthesis of androgens in the adrenal glands and prostate tumor tissue. Dexamethasone, a potent synthetic glucocorticoid, is used in this regimen to provide necessary corticosteroid replacement (as ketoconazole also inhibits cortisol synthesis) and to suppress the secretion of adrenocorticotropic hormone (ACTH) from the pituitary gland. By suppressing ACTH, dexamethasone reduces the stimulus for adrenal androgen production, potentially overcoming resistance observed with other corticosteroid combinations like ketoconazole and hydrocortisone. This specific regimen was evaluated in a Phase II clinical trial led by the University of California, San Francisco (UCSF) to determine if switching the corticosteroid component could slow or reverse disease progression in patients with progressive CRPC.

Other names

ketoconazole/dexamethasoneKeto/Dexketoconazole and dexamethasone