Adjuvant Mitotane for Adrenocortical Cancer—A Recurring Controversy

Adrenocortical cancer (ACC) is a tumor with a high mortality, often complicated by hypercortisolism. Because of its rarity, physicians must rely on anecdotal evidence, uncontrolled trials, and retrospective studies. Mitotane is the only drug approved by the U.S. Food and Drug Administration for ACC. Interest in mitotane dates to the 1960s when studies demonstrated its ability to 1) inhibit adrenocortical steroid biosynthesis by inhibiting cholesterol side chain cleavage and 11 β-hydroxylation and 2) affect extraadrenal disposition of cortisol by inducing hepatic clearance (1,2). Over the years, mitotane has been at the center of many controversies because of its limited efficacy and associated toxicities. In this opinion, we address the use of adjuvant mitotane in ACC, a recurring controversy again under debate (3,4).