Practical treatment using mitotane for adrenocortical carcinoma

Curr Opin Endocrinol Diabetes Obes. 2014 Jun;21(3):159-65. doi: 10.1097/MED.0000000000000056.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adrenal Cortex Neoplasms / drug therapy*
  • Adrenal Cortex Neoplasms / mortality
  • Adrenocortical Carcinoma / drug therapy*
  • Adrenocortical Carcinoma / mortality
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Chemotherapy, Adjuvant / methods
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Female
  • Humans
  • Male
  • Mitotane / administration & dosage*
  • Mitotane / therapeutic use*
  • Neoplasm Recurrence, Local / prevention & control
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Hormonal
  • Mitotane