Extraordinary response to mitotane monotherapy in advanced aggressive adrenocortical carcinoma

Adrenocortical carcinoma (ACC) is an aggressive tumor; the 5-year overall survival rate for advanced disease is <15%. First-line therapy for advanced disease is mitotane, either as monotherapy or in combination with chemotherapy. Overall survival after these strategies is comparable when used in the appropriate subgroup of patients. Mitotane monotherapy is usually reserved for biologically low-risk tumors, with a reported partial response rate of 13% to 31%. Typically, responses are observed when mitotane plasma levels are >14 mg/L, but sometimes partial and complete responses have been reached with lower levels. No single clinical or pathological factor has been extensively validated to predict the response to mitotane monotherapy. We describe the case of a 45-year-old patient with metastatic, rapidly growing, unresectable ACC who had a remarkable response to mitotane monotherapy. After 4 months, a 45% reduction of the primary tumor and regression of lung metastases were observed, despite plasmatic mitotane levels of 5 mg/L. Mitotane may represent an effective therapy in selected cases of advanced ACC and despite plasma levels <14 mg/L.