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Practical treatment using mitotane for adrenocortical carcinoma

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

Current Opinion in Endocrinology, Diabetes & Obesity: June 2014 - Volume 21 - Issue 3 - p 159–165
doi: 10.1097/MED.0000000000000056
ADRENAL CORTEX AND MEDULLA: Edited by Anand Vaidya

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.

aInternal Medicine I

bPharmacology, Department of Clinical and Biological Sciences, University of Turin, Italy

Correspondence to M. Terzolo, MD, Internal Medicine I, Department of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga Hospital, Regione Gonzole, 10 10043 Orbassano, Italy. Tel: +39 011 9026788; fax: +39 011 6705456; e-mail: terzolo@usa.net

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins