Adverse events related to mitotane during treatment of adrenocortical carcinoma.

Mitotane is a drug widely indicated in patients with adrenocortical carcinoma. Several adverse events related to mitotane have been reported in 30 to 90% of patients. We present a case series of toxicities related to mitotane therapy and their management. Clinical and laboratory examinations to detect adverse events were carried out at baseline, monthly for the first six months and quarterly afterwards. Mitotane blood concentrations were measured by liquid chromatography. Six patients diagnosed with adrenocortical carcinoma and treated with mitotane were included, with hormone overproduction in four of them. Median time of follow up during mitotane therapy was 13 months [5-36]. All had adverse events related to mitotane detected during the first three months of treatment (median mitotane dose at first adverse event: 2 g/day). Four patients presented two or more adverse events. Endocrine side effects were the most frequently found (adrenal insufficiency, followed by hypothyroidism and hypercholesterolemia in order of frequency). Replacement therapy and/or statin treatment was prescribed as needed. Mitotane blood concentration in 3 of 4 patients was below the optimal range. Treatment with mitotane requires individualized care to mitigate the risks of adverse events, optimize therapeutic outcomes, and ensure patient safety.