Clinical results of the use of mitotane for adrenocortical carcinoma

Mitotane (o,p'-DDD) acts mainly as an inhibitor of intramitochondrial pregn enolone 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 u sed for 40 years in the treatment of adrenocortical carcinoma, mainly its r egional and metastatic stage, as an adjuvant to surgical resection of the t umor. 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 ef ficient than when administered later. We have administered this drug in all cases of microscopically confirmed adrenocortical carcinoma, irrespectivel y of stage at the time of surgery, for fear of a false too optimistic class ification. In our series of 82 patients with adrenocortical carcinoma, 59 p atients have been treated with mitotane, 32 of them immediately after surge ry, 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 on ly 6 survivors in the group receiving mitotane with a delay. All patients w ere simultaneously given replacement therapy. Undesired effects of mitotane administration included increased aminotransferase and alkaline phosphatas e activity, decreased white cell, platelet or red cell number, and myasthen ia. Furthermore, we used mitotane with good results in Gushing's syndrome o f nonmalignant origin as pre-treatment before surgery or in long-term treat ment for patients with poor tolerance of other adrenal inhibitors.