Endocrine Abstracts

Adrenocortical carcinoma (ACC) is a rare endocrine tumour with a generally poor prognosis. Mitotane is the only approved drug for treatment of advanced ACC (“palliative” setting). However, response is relatively poor with up to 20% of patients experiencing objective response (Megerle 2018). Moreover, adjuvant treatment with mitotane is frequently recommended for patients at high risk of disease recurrence after surgery (Terzolo 2007, Fassnacht 2018). Of note, mitotane is a difficult drug to manage, with a long half-life, a narrow therapeutic window and a high degree of dose-limiting toxicity. In fact, mitotane is associated with several adverse events, including adrenal insufficiency, gastrointestinal-, central nervous system-, liver- and other endocrine-related. Also, mitotane interferes with the metabolism of several medications due to the activation of the liver enzyme CYP3A4. Currently, there are no reliable biomarkers predictive of response to treatment, mitotane plasma levels greater than 14 mg/L have been associated with longer survival (Hermsen 2011, Puglisi 2019, Puglisi 2020). Therefore, the management of patients under treatment with mitotane requires careful evaluation and frequent monitoring, which should be carried out in an expert centre. During the session, I will summarise the recommendation for the management of patients treated with mitotane, according to the current European Guidelines (Fassnacht 2018 and 2020). This will include the following points:

1. Choice of initial mitotane dose regimen

2. Hydrocortisone replacement treatment

3. Regular monitoring by clinical assessment and surveillance blood tests

○ U&E, liver function, blood count and plasma mitotane concentrations (initially every 3–4 weeks, then every 2–3 months).

○ Plasma renin, thyroid function, testosterone (in males), lipid profile should be monitored every 3-4 months.

1. Mitotane dose titration

2. Mitotane treatment duration