Consensus on the Treatment of Adrenocortical Carcinoma with Mitotane(2021)

Adrenocortical carcinoma (ACC) is a rare malignant tumor that occurs in the adrenal cortex, and surgery is the first choice for treating ACC. Medical therapy and radiotherapy are adjuvant treatments for patients with unresectable metastasized tumors or incomplete resection. Mitotane is the only adrenergic cytotoxic drug approved by the American Food and Drug Administration and European Medicines Agency for the treatment of ACC by inhibiting mitochondrial respiration, causing mitochondrial membrane dysfunction and inducing endoplasmic reticulum stress, and it reduces the secretory function of ACC cells by inhibiting the function and expression of several enzymes in the adrenocortical steroidogenesis pathway. Mitotane is recommended as the first choice for adjuvant therapy by multiple international guidelines and consensus. During treatment with mitotane, its blood concentration should be maintained between 14 to 20 mg/L, while the related adverse drug reactions and drug-drug interactions should also be monitored. To promote further standardization of the clinical application of mitotane, and to ensure the effectiveness and safety of mitotane, Peking Union Medical College Hospital relied on the multi-disciplinary team for the diagnosis and treatment of rare diseases, organized experts and scholars in related fields to discuss and modify many times, and finally formed this consensus for clinicians' reference.