Mitotane for adrenocortical carcinoma treatment.

Adrenocortical carcinoma (ACC) is a rare neoplasm with poor prognosis. Mitotane is the only adrenal-specific agent available for the treatment of ACC, and although it has been used for several decades, many of its pharmacological properties, as well as its exact mechanism of action, remain to be fully elucidated. It is known that metabolic activation is essential for the adrenolytic activity of mitotane. Most published clinical reports of mitotane use are retrospective analyses of small numbers of patients, however, the collective findings of these studies indicate that mitotane has activity against ACC; in approximately 25% of cases mitotane led to an objective tumor regression and, in the majority of patients, control of hormone excess could be achieved. Side effects occur frequently during mitotane treatment and they mainly affect the gastrointestinal tract and the central nervous system. As not all patients respond to mitotane therapy, it is one of the challenges for the future to define the subset of patients who do respond to mitotane to avoid treatment of patients who are unlikely to respond to this toxic drug. The pharmacological properties of mitotane and its efficacy in the treatment of ACC are analyzed in this review.