What are the specific functions and efficacy of mitotane?

Mitotane is a chemotherapy drug specifically used to treat adrenocortical cancer (Adrenocortical Carcinoma, ACC). Its most significant mechanism of action is to selectively inhibit the function and survival of adrenocortical cells. Mitotane is an organochlorine derivative with a DDT-like structure. It can selectively destroy adrenocortical tissue in the body, especially the zona fasciculata and zona reticularis cells, thereby inhibiting the synthesis of glucocorticoids and sex hormones. This feature makes it particularly suitable for endocrine-active ACC patients. By controlling the symptoms of Cushing's syndrome or androgen excess caused by excess hormone secretion, it can quickly alleviate the patient's clinical manifestations, such as hyperglycemia, hypertension, hirsutism, menstrual disorders, etc.

From an anti-tumor perspective, mitotane can delay tumor progression by inducing cell apoptosis, inhibiting cancer cell proliferation. Although its cytotoxicity is milder than traditional chemotherapy drugs, mitotane has shown longer progression-free survival (PFS) and partial objective response rate (ORR) in a rare and rapidly progressing tumor type like ACC. Especially in patients with postoperative adjuvant therapy or recurrence/metastasis, mitotane can significantly reduce the local recurrence rate and the risk of distant metastasis, and is currently the first-line systemic treatment drug recommended in international guidelines.

In addition, mitotane has unique pharmacokinetic characteristics. It is highly fat-soluble and easily accumulates in adipose tissue, extending its biological half-life to weeks to months. This long-term stable blood drug concentration is conducive to maintaining sustained anti-tumor effect, but it is also necessary to regularly monitor the blood drug concentration (it is recommended to maintain it at 14-20μg/mL) to avoid the accumulation of toxicity. In general, the main functions of mitotane include inhibiting adrenal hormone synthesis, shrinking or stabilizing tumors, and delaying disease progression. It is a highly valuable specific drug in the treatment of ACC.

Reference materials:https://go.drugbank.com/drugs/DB00648