Mitotane (
o,p'-DDD) acts mainly as an inhibitor of intramitochondrial
pregnenolone and
cortisol synthesis. Its adrenolytic effect depends on metabolic activation due to conversion to
o,p'-DDA and
o,p'-DDE. The
drug has been used for 40 years in the treatment of
adrenocortical carcinoma, mainly its regional and metastatic stage, as an adjuvant to surgical resection of the
tumor. In the medical literature there are controversial opinions about its efficacy for the treatment of
adrenocortical carcinoma. In our experience,
mitotane administered immediately after surgery appeared to be much more efficient than when administered later. We have administered this
drug in all cases of microscopically confirmed
adrenocortical carcinoma, irrespectively of stage at the time of surgery, for fear of a false too optimistic classification. In our series of 82 patients with
adrenocortical carcinoma, 59 patients have been treated with
mitotane, 32 of them immediately after surgery, and 27 with a delay of 2 to 24 months. Today there are 18 survivors in the group of patients treated with
mitotane soon after the operation and only 6 survivors in the group receiving
mitotane with a delay. All patients were simultaneously given replacement
therapy. Undesired effects of
mitotane administration included increased
aminotransferase and
alkaline phosphatase activity, decreased white cell, platelet or red cell number, and myasthenia. Furthermore, we used
mitotane with good results in
Cushing's syndrome of non-malignant origin as pre-treatment before surgery or in long-term treatment for patients with poor tolerance of other adrenal inhibitors.