Mitotane

Mitotane (brand Lysodren) is an oral antineoplastic agent with adrenolytic properties, used primarily to treat adrenocortical carcinoma (ACC). It is a derivative of the pesticide DDT (o,p'-DDD).

Mechanism: Mitotane targets adrenal cortical cells, causing selective cytotoxicity and atrophy of the zona fasciculata and reticularis, reducing cortisol and other adrenal steroids. The precise mechanism is not fully understood and may involve disruption of mitochondrial function and steroidogenesis.

Clinical use: It is indicated for advanced, unresectable, or metastatic ACC and is sometimes used to control hypercortisolism in adrenal Cushing syndrome. Therapy is usually combined with surgery or radiotherapy when possible and requires long-term administration with careful monitoring.

Administration and monitoring: Given orally in divided doses with gradual dose-escalation to achieve therapeutic plasma concentrations. Plasma mitotane levels guide dosing; steady-state levels may take weeks to months due to a long half-life. Adverse effects are common and include nausea, vomiting, diarrhea, fatigue, ataxia, dizziness, skin rash, and hepatic toxicity; neurotoxicity and adrenal insufficiency can occur, necessitating glucocorticoid and mineralocorticoid replacement and regular lab tests (liver function, thyroid function) and dose adjustments. Mitotane induces metabolic enzymes and has notable drug interactions (e.g., with anticoagulants, anticonvulsants). It is teratogenic and contraindicated in pregnancy.

Prognosis: Response rates vary; benefit is often modest in ACC and treatment is part of multidisciplinary care; discontinuation is considered if toxicity outweighs benefit.