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Pharmacological profile and effects of mitotane in adrenocortical carcinoma
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  • Claudia Corso,
  • Alexandra Acco,
  • Camila Bach,
  • Sandro Bonatto,
  • Bonald Figueiredo,
  • Lauro Souza
Claudia Corso
Instituto de Pesquisa Pelé Pequeno Príncipe
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Alexandra Acco
Federal University of Parana
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Camila Bach
Instituto de Pesquisa Pelé Pequeno Príncipe
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Sandro Bonatto
Instituto de Pesquisa Pelé Pequeno Príncipe
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Bonald Figueiredo
Instituto de Pesquisa Pelé Pequeno Príncipe
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Lauro Souza
Instituto de Pesquisa Pelé Pequeno Príncipe
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Abstract

Mitotane is the only drug approved for treating adrenocortical carcinoma (ACC) by the FDA since 1959, despite the controversy regarding its efficacy in prolonging patient survival. This drug has cytotoxic effects on tumor tissue by inducing cell death and antisecretory effects on adrenal cells by inhibiting the synthesis of adrenocortical steroids involved in the pathogenesis of ACC. To reach the therapeutic plasma concentration, high doses of mitotane are usually necessary, which may result in several adverse effects. This suggests that important pharmacological features are involved in the mechanisms of action of this drug, such as first pass metabolism, tissue accumulation, and extensive time needed for drug elimination. However, few studies have reported the pharmacological aspects of mitotane, and they did not provide sufficient evidence regarding monitoring mitotane’s therapeutic effects. Therefore, this review summarized the chemistry, pharmacokinetics and pharmacodynamics, therapeutic effects, toxic effects, and new perspectives of mitotane treatment that are currently under investigation. Understanding the pharmacological profile of mitotane can improve the monitoring and efficacy of this drug in ACC treatment and can further provide useful information for the development of new drugs with specific action against ACC with fewer adverse effects.

Peer review status:IN REVISION

27 May 2020Submitted to British Journal of Clinical Pharmacology
28 May 2020Assigned to Editor
28 May 2020Submission Checks Completed
26 Jun 2020Reviewer(s) Assigned
16 Aug 2020Review(s) Completed, Editorial Evaluation Pending
18 Aug 2020Editorial Decision: Revise Major