How close are we to personalized mitotane dosing in the treatment of adrenocortical carcinoma? State of the art and future perspectives

R.V. Steenaard, M.H.T. Ettaieb, T.M.A. Kerkhofs, H.R. Haak*

*Corresponding author for this work

Research output: Contribution to journal(Systematic) Review article peer-review

Abstract

Introduction Mitotane is the only drug registered specifically for adrenocortical carcinoma. Finding the optimal dose for a patient is difficult due to large differences in bioavailability, toxicity and effect. We therefore look to improve personalized dosing of mitotane. Areas covered We searched PubMed for studies related to mitotane dosing, pharmacokinetics, pharmacogenetics and combination therapy. Comparison of different dosing strategies have not resulted in an optimal advice. Several computerized pharmacokinetic models have been proposed to predict plasma levels. The current pharmacokinetic models do not explain the full variance in plasma levels. Pharmacogenetics have been proposed to find the unexplained variance. Studies on combination therapy have not yet led to a potential dose adjustment for mitotane. Expert opinion Computerized pharmacokinetics models are promising tools to predict plasma levels, further validation is needed. Pharmacogenetics are introduced in these models, but more research is required before clinical application. We believe that in the near future, personalized mitotane dosage will be aided by a validated web-based pharmacokinetic model with good predictive ability based primarily on clinical characteristics, adjustable for actual plasma levels and dosage.
Original languageEnglish
Pages (from-to)677-683
Number of pages7
JournalExpert Opinion on Drug Metabolism & Toxicology
Volume17
Issue number6
DOIs
Publication statusPublished - 3 Jun 2021

Keywords

  • Adrenocortical carcinoma
  • mitotane
  • personalized treatment
  • pharmacokinetics
  • pharmacogenetics
  • CYTOTOXIC ACTIVITY
  • ER STRESS
  • IN-VITRO
  • PLASMA
  • CANCER
  • ACTIVATION
  • O,P'-DDD
  • COMBINATION
  • METABOLITES
  • MODULATION

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