Impact of adjuvant mitotane on the clinical course of patients with adrenocortical cancer

Abstract

Background. Adrenocortical carcinoma is a rare and aggressive disease with a poor prognosis. Adjuvant mitotane administration has been suggested as a strategy that might improve the outcome of patients with localized disease. Methods. The authors analyzed the clinical outcome of patients with localized or regional adrenocortical cancer. The study included 19 patients who were registered at M. D. Anderson Cancer Center during a 3‐year period and who had localized or regional disease at the time of surgery. Of these, eight patients received mitotane postoperatively and continued the drug until their last contact or recurrence (Group A, adjuvant); five patients began taking mitotane after surgery but discontinued it after 2–12 months for reasons unrelated to the disease (Group P, postoperative); and six patients did not receive mitotane (Group N, no mitotane). All patients have been followed for at least 12 months. Results. The treatment groups differed significantly in their time to recurrence; the disease‐free interval was shortest in Group A (P = 0.0055, by log‐rank test). There was no statistical difference in survival among the groups, but the profile remained unfavorable for Group A. The 2‐year survival rate was 100% for Groups N and P but only 43% for Group A. Of the potentially confounding factors, gender, age, steroid hypersecretion, and tumor size, none had any influence on recurrence or survival rates. Conclusions. These findings do not support the conclusion that adjuvant mitotane is beneficial in patients with localized or regional adrenocortical cancer. Neither the disease‐free interval nor survival was improved by the drug. The authors suggest that alternative therapeutic strategies be explored for the management of these patients.

Prospective evaluation of mitotane toxicity in adrenocortical cancer patients treated adjuvantly

“…The use of rather low doses of mitotane (up to 6 g daily) may explain why mitotane-related toxicity was acceptable (Kasperlik-Zaluska et al 1995, Dickstein et al 1998, while severe and disabling toxicity was reported in the studies where high, rapidly increasing, daily doses of mitotane were employed (Vassilopoulou-Sellin et al 1993, Schulick & Brennan 1999. In our series, all the patients experienced elevation of aPH and gGT and most patients reported also gastrointestinal Endocrine-Related Cancer (2008) 15 1043-1053 www.endocrinology-journals.org symptoms, but gastrointestinal and hepatic toxicities were of grade 1 in most cases.…”

A phase II trial of combination chemotherapy and surgical resection for the treatment of metastatic adrenocortical carcinoma

“…11,12,20 In the current study, this complication was treated by the administration of daily hydrocortisone, and when indicated, supplemental fluorohydrocortisone. In the first few patients, replacement therapy was not initiated until there was clinical evidence of adrenal insufficiency or a high adrenocorticotropic hormone level was documented.…”

Management of adjuvant mitotane therapy following resection of adrenal cancer

“…This concept coupled with a limited evidence of efficacy in the literature published since recently [5][6][7][8][13][14][15][16][17] made adjunctive treatment with mitotane progressively less appealing. As a matter of fact, no recommendation in favor or against adjuvant treatment was formulated at a consensus conference on ACC held at Ann Arbor in 2003 [18].…”