Mitotane ( o, p′-DDD)

Abstract

Summary Mitotane ( o, p′ -DDD) is an isomer of the insecticide DDD and a chemical congener of the insecticide DDT. Its use in the treatment of unresectable adrenal cortical carcinoma was based upon the initial observation of Nelson and Woodward that dogs given the insecticide DDT showed necrosis and atrophy of the adrenal cortex. Mitotane exerts a direct cytotoxic effect on the fascicular and reticular zones of the adrenal cortex. Following intravenous and oral administration, varying concentrations are demonstrable in different tissues and organs like the adipose tissue, adrenals and liver. The compound is excreted in the stool and urine. Clinical trials in 301 patients with inoperable adrenal cortical carcinoma have demonstrated its therapeutic efficacy characterized by objective evidence of tumor regression, decreased steroid excretion and improvement in subjective symptomatology. Toxicities from mitotane are referrable to the gastrointestinal, neuromuscular and dermal systems. Less common side effects involve the eyes, gonitourinary and cardiovascular systems. They are reversible upon reduction of the dose or discontinuation of the drug. The recommended dose schedule is to start the patient at 8–10 g/day in divided doses. The dose should be reduced if severe side effects develop. It has been suggested that steroid replacement therapy be administered concomitantly with the start of mitotane treatment (12, 19) rather than after the appearance of signs of adrenocortical insufficiency or when urinary corticoid excretion is low (2). Though there are no reported data on the use of mitotane following surgical removal of an adrenocortical carcinoma, its potential value as an adjuvant agent (inasmuch as some of these patients subsequently develop recurrence or metastases) deserves some consideration in the future.