Clinical results of the use of mitotane for adrenocortical carcinoma

Abstract

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 Cushings syndrome of nonmalignant origin as pre-treatment before surgery or in long-term treatment for patients with poor tolerance of other adrenal inhibitors. Correspondence

Adjunctive treatment of adrenocortical carcinoma

“…First, most studies [5,[12][13][14][15] had limited statistical powers to conduct a reliable evaluation of the treatment efficacy. In fact, only four groups reported the outcome of adjuvant mitotane treatment in series of more than 20 patients.…”

“…Second, many studies [5,8,[13][14][15][16][17] did not include a concomitant control group of untreated patients with comparable baseline characteristics, whereas in some series a number of patients underwent multiple adjuvant treatments in various sequences [7,14]. In addition, the Purpose of review Description of the adjunctive treatment strategies in patients with adrenocortical carcinoma after complete surgical resection.…”

Etoposide, doxorubicin and cisplatin plus mitotane in the treatment of advanced adrenocortical carcinoma: a large prospective phase II trial

“…The adrenolytic drug mitotane (1,1 dichloro-2 (o-chlorophenyl)-2-(p-chloro-phenyl) etane) has been widely employed but it is difficult to appraise its efficacy from retrospective studies which have seldom used standard criteria to assess objective responses (Luton et al 1990). Transient partial responses were found in 19 to 34% of cases, whereas complete responses were anecdotal (Wooten & King 1993, Haak et al 1994, Kasperlik-Zaluska 2000, Terzolo et al 2000, Baudin et al 2001. The toxicity of mitotane is admittedly a major limitation to its use.…”

Successful treatment of adrenocortical carcinoma with pulmonary metastasis in a child: Report of a case

“…It is also capable of producing selective adrenocortical necrosis both in the ACC primary tumor and in metastases. 12 However, the role of adjuvant chemotherapy with mitotane remains controversial and pediatric dosages have not been established. 4 The staging system of ACC 13 (I to IV) refl ects its natural history.…”