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Current Opinion in Endocrinology, Diabetes & Obesity:
doi: 10.1097/MED.0000000000000056
ADRENAL CORTEX AND MEDULLA: Edited by Anand Vaidya

Practical treatment using mitotane for adrenocortical carcinoma

Terzolo, Massimoa; Zaggia, Barbaraa; Allasino, Barbaraa; De Francia, Silviab

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Abstract

Purpose of review: Description of novel findings about the mechanism of action of mitotane and its activity as an adjunctive postoperative measure, or for treatment of advanced adrenocortical carcinoma.

Recent findings: Several in-vitro studies have shown that mitotane suppresses gene transcription of different enzymatic steps of the steroidogenetic pathway. Moreover, mitotane induces CYP3A4 expression, thus accelerating the metabolic clearance of a variety of drugs including steroids. Retrospective studies provided evidence that adjunctive mitotane can prolong recurrence-free survival of treated patients. The concept of a therapeutic window of mitotane plasma concentrations was confirmed also for adjunctive treatment, but the relationship between mitotane concentration and given dose is loose. Genetic variability of the P450-dependent enzymes metabolizing mitotane may explain individual differences.

Summary: Mitotane concentration of 14–20 mg/l should be reached and maintained during treatment also in an adjunctive setting. In advanced adrenocortical carcinoma, a high-dose starting regimen should be employed when mitotane is used as monotherapy. The combination of mitotane with other drugs should consider the possibility of pharmacologic interactions due to mitotane-induced activation of drug metabolism. This concept applies also to steroid replacement in mitotane-treated patients, who need higher doses to adjust for increased steroid metabolism.

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins

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