Mitotane’s role in the management of adrenocortical carcinoma

Adrenocortical carcinoma (ACC) is a rare but aggressive malignancy with high postoperative recurrence rates and poor prognosis. Mitotane remains the only approved agent for ACC, exerting antitumor effects by disrupting mitochondrial integrity, inhibiting steroidogenic enzymes, and interfering with cholesterol metabolism.

Clinical evidence supports maintaining plasma concentrations between 14–20 mg/L to maximize efficacy while minimizing toxicity. This comprehensive review outlines mitotane's mechanisms of action, clinical applications in adjuvant and advanced settings, dosage strategies, therapeutic drug monitoring approaches, and management of frequent adverse effects. It also discusses emerging combination strategies with chemotherapy and immunotherapy, highlighting the need for personalized treatment and further research into novel therapeutic combinations.