Pharmacokinetic variability of mitotane in pediatric adrenocortical carcinoma and the role of CYP2B6 genotypes: a pediatric case series

Ivy A.E. Ankone; Tirsa de Kluis; Lidwien M. Hanff; Antoinette Jaspers-Bakker; Ronald R. de Krijger; Jesse J. Swen; Kathalijne A. Oudhoff; Marieke J.M. Meijs; Max M. van Noesel; Alwin D.R. Huitema; Meta H.M. Diekstra

doi:10.1016/j.ejcped.2026.100499

Pharmacokinetic variability of mitotane in pediatric adrenocortical carcinoma and the role of CYP2B6 genotypes: a pediatric case series

Ivy A.E. Ankone
, Tirsa de Kluis
, Lidwien M. Hanff
, Antoinette Jaspers-Bakker
, Ronald R. de Krijger
, Jesse J. Swen
, Kathalijne A. Oudhoff
, Marieke J.M. Meijs
, Max M. van Noesel
, Alwin D.R. Huitema
, Meta H.M. Diekstra^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Despite therapeutic drug monitoring of mitotane, achieving target plasma concentrations remains challenging. Commonly reported enzymes involved in mitotane metabolism are cytochrome P450 (CYP)3A4 and 2B6, with CYP2B6 being highly polymorphic. We evaluated the impact of CYP2B6 genotypes on achieving therapeutic concentrations in six patients. We observed intermediate, normal, and rapid metabolizer genotypes. Intermediate or normal metabolizers all reached therapeutic concentrations, receiving between 3.5–5.5 g/m²/day. The rapid metabolizer did not reach therapeutic concentrations despite receiving up to 8.0 g/m²/day. These results indicate CYP2B6 genotypes may affect the dose needed to achieve and maintain therapeutic concentrations of mitotane in pediatric adrenocortical carcinoma.

Original language	English
Article number	100499
Journal	EJC Paediatric Oncology
Volume	7
DOIs	https://doi.org/10.1016/j.ejcped.2026.100499
Publication status	Published - Jun 2026

Keywords

Adrenocortical carcinoma
Cancer
Cytochrome P-450 CYP2B6
Mitotane
Pediatrics

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Ankone, I. A. E., de Kluis, T., Hanff, L. M., Jaspers-Bakker, A., de Krijger, R. R., Swen, J. J., Oudhoff, K. A., Meijs, M. J. M., van Noesel, M. M., Huitema, A. D. R., & Diekstra, M. H. M. (2026). Pharmacokinetic variability of mitotane in pediatric adrenocortical carcinoma and the role of CYP2B6 genotypes: a pediatric case series. EJC Paediatric Oncology, 7, Article 100499. https://doi.org/10.1016/j.ejcped.2026.100499

@article{8c8ac0484c414948a4b130a00991c8a7,

title = "Pharmacokinetic variability of mitotane in pediatric adrenocortical carcinoma and the role of CYP2B6 genotypes: a pediatric case series",

abstract = "Despite therapeutic drug monitoring of mitotane, achieving target plasma concentrations remains challenging. Commonly reported enzymes involved in mitotane metabolism are cytochrome P450 (CYP)3A4 and 2B6, with CYP2B6 being highly polymorphic. We evaluated the impact of CYP2B6 genotypes on achieving therapeutic concentrations in six patients. We observed intermediate, normal, and rapid metabolizer genotypes. Intermediate or normal metabolizers all reached therapeutic concentrations, receiving between 3.5–5.5 g/m2/day. The rapid metabolizer did not reach therapeutic concentrations despite receiving up to 8.0 g/m2/day. These results indicate CYP2B6 genotypes may affect the dose needed to achieve and maintain therapeutic concentrations of mitotane in pediatric adrenocortical carcinoma.",

keywords = "Adrenocortical carcinoma, Cancer, Cytochrome P-450 CYP2B6, Mitotane, Pediatrics",

author = "Ankone, \{Ivy A.E.\} and \{de Kluis\}, Tirsa and Hanff, \{Lidwien M.\} and Antoinette Jaspers-Bakker and \{de Krijger\}, \{Ronald R.\} and Swen, \{Jesse J.\} and Oudhoff, \{Kathalijne A.\} and Meijs, \{Marieke J.M.\} and \{van Noesel\}, \{Max M.\} and Huitema, \{Alwin D.R.\} and Diekstra, \{Meta H.M.\}",

note = "Publisher Copyright: {\textcopyright} 2026 The Authors",

year = "2026",

month = jun,

doi = "10.1016/j.ejcped.2026.100499",

language = "English",

volume = "7",

journal = "EJC Paediatric Oncology",

issn = "2772-610X",

publisher = "Elsevier",

}

Ankone, IAE, de Kluis, T, Hanff, LM, Jaspers-Bakker, A, de Krijger, RR, Swen, JJ, Oudhoff, KA, Meijs, MJM, van Noesel, MM , Huitema, ADR & Diekstra, MHM 2026, 'Pharmacokinetic variability of mitotane in pediatric adrenocortical carcinoma and the role of CYP2B6 genotypes: a pediatric case series', EJC Paediatric Oncology, vol. 7, 100499. https://doi.org/10.1016/j.ejcped.2026.100499

TY - JOUR

T1 - Pharmacokinetic variability of mitotane in pediatric adrenocortical carcinoma and the role of CYP2B6 genotypes

T2 - a pediatric case series

AU - Ankone, Ivy A.E.

AU - de Kluis, Tirsa

AU - Hanff, Lidwien M.

AU - Jaspers-Bakker, Antoinette

AU - de Krijger, Ronald R.

AU - Swen, Jesse J.

AU - Oudhoff, Kathalijne A.

AU - Meijs, Marieke J.M.

AU - van Noesel, Max M.

AU - Huitema, Alwin D.R.

AU - Diekstra, Meta H.M.

PY - 2026/6

Y1 - 2026/6

N2 - Despite therapeutic drug monitoring of mitotane, achieving target plasma concentrations remains challenging. Commonly reported enzymes involved in mitotane metabolism are cytochrome P450 (CYP)3A4 and 2B6, with CYP2B6 being highly polymorphic. We evaluated the impact of CYP2B6 genotypes on achieving therapeutic concentrations in six patients. We observed intermediate, normal, and rapid metabolizer genotypes. Intermediate or normal metabolizers all reached therapeutic concentrations, receiving between 3.5–5.5 g/m2/day. The rapid metabolizer did not reach therapeutic concentrations despite receiving up to 8.0 g/m2/day. These results indicate CYP2B6 genotypes may affect the dose needed to achieve and maintain therapeutic concentrations of mitotane in pediatric adrenocortical carcinoma.

AB - Despite therapeutic drug monitoring of mitotane, achieving target plasma concentrations remains challenging. Commonly reported enzymes involved in mitotane metabolism are cytochrome P450 (CYP)3A4 and 2B6, with CYP2B6 being highly polymorphic. We evaluated the impact of CYP2B6 genotypes on achieving therapeutic concentrations in six patients. We observed intermediate, normal, and rapid metabolizer genotypes. Intermediate or normal metabolizers all reached therapeutic concentrations, receiving between 3.5–5.5 g/m2/day. The rapid metabolizer did not reach therapeutic concentrations despite receiving up to 8.0 g/m2/day. These results indicate CYP2B6 genotypes may affect the dose needed to achieve and maintain therapeutic concentrations of mitotane in pediatric adrenocortical carcinoma.

KW - Adrenocortical carcinoma

KW - Cancer

KW - Cytochrome P-450 CYP2B6

KW - Mitotane

KW - Pediatrics

UR - https://www.scopus.com/pages/publications/105031745187

U2 - 10.1016/j.ejcped.2026.100499

DO - 10.1016/j.ejcped.2026.100499

M3 - Article

AN - SCOPUS:105031745187

SN - 2772-610X

VL - 7

JO - EJC Paediatric Oncology

JF - EJC Paediatric Oncology

M1 - 100499

ER -

Pharmacokinetic variability of mitotane in pediatric adrenocortical carcinoma and the role of CYP2B6 genotypes: a pediatric case series

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