Abiraterone acetate: a promising drug for the treatment of castration-resistant prostate cancer.
Abiraterone acetate (CB7630), a pregnenolone analog, is an orally administered small molecule that irreversibly inhibits a rate-limiting enzyme in androgen biosynthesis, CYP17, and blocks the synthesis of androgens in the testes, adrenal glands and prostate without causing adrenal insufficiency. In clinical studies, abiraterone acetate is well tolerated and shows promising clinical activity in castration-resistant prostate cancer. The recommended Phase II dose of abiraterone acetate is 1000 mg orally daily in combination with prednisone 5 mg twice daily. Side effects are minimal and mostly associated with secondary mineralocorticoid excess, owing to a compensatory increase in upstream steroids, such as deoxycorticosterone and corticosterone. These include hypertension, hypokalemia and edema and are easily manageable with a selective mineralocorticoid antagonist, such as eplerenone, or low-dose corticosteroids. Currently, abiraterone acetate is being tested in a Phase III trial for men with progressive castration-resistant prostate cancer who are chemotherapy naive. A Phase III trial for patients following prior chemotherapy has been completed and is awaiting analysis.
Agarwal
Neeraj
N
Huntsman Cancer Institute, University of Utah, Salt Lake City, 2000 Circle of Hope, Ste 2123, UT 84117, USA.
Hutson
Thomas E
TE
Vogelzang
Nicholas J
NJ
Sonpavde
Guru
G
D000726:Androgen Antagonists / Q000627:therapeutic use; D000736:Androstenes; D000737:Androstenols / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy*
D000726:Androgen Antagonists; D000736:Androstenes; D000737:Androstenols; D000970:Antineoplastic Agents; C089740:abiraterone