EDP-mitotane in children: reassuring evidence of reversible side-effects and neurotoxicity

Adrenocortical carcinoma affects one in 5 million children each year. Since prognosis for children older than 4 years is limited, clinicians often choose aggressive treatment with etoposide, doxorubicin, cisplatin (EDP) and mitotane after resection. However, little is known about the impact of EDP-mitotane in children. We provide an overview of case-reports and case series listing side-effects and neurotoxicity of EDP-mitotane in children. Fourteen studies were identified describing a range of gastro-intestinal, endocrine, developmental and neuropsychological side-effects. Neurotoxicity included motor- and speech delay, decreased concentration and lower school performance. These side-effects appear to be reversible after mitotane discontinuation. We have added our own experience with a 10 year old girl with advanced adrenocortical carcinoma treated with EDP and 2 years of mitotane after irradical resection. She developed an impactful, but reversible, decrease in cognitive development measured by a standardized neuropsychological assessment before, during and after mitotane therapy. This decrease was mostly measurable in terms of decreased processing speed and concentration and a significant drop in school performance. Combined with fatigue and insecurity, this caused problems in short-term memory and the need to change her school type. In conclusion, EDP-mitotane is associated with several side-effects including neurotoxicity in pediatric cases, all reversible after mitotane discontinuation.