title: Cytotoxic treatment of adrenocortical carcinoma.
abstract: Adrenocortical carcinoma (ACC) is a rare, aggressive tumor that is often detected in an advanced stage. Medical treatment with the adrenotoxic drug mitotane has been used for decades, but critical prospective trials on its role in residual disease or as an adjuvant agent after surgical resection are still lacking. The concept of a critical threshold plasma level of the drug must be confirmed in controlled studies. Because individual responsiveness cannot be predicted, the use mitotane is still advised for nonresectable disease. In case of cortisol or other steroid overproduction, several drugs (e.g., ketoconazole or aminoglutethimide) may be used. Chemotherapy with single agents (e.g., doxorubicin or cisplatin) have been disappointing, with low response rates (< 30%) and a short response duration. Part of this refractoriness may be explained by the fact that ACC tumors express the multidrug-resistance gene MDR-1. Chemotherapy with multiple agents has been tested in smaller series and has resulted in significant side effects. The best results were achieved by the combination of etoposide, doxorubicin, and cisplatin associated with mitotane, achieving a response rate of 54%, including individual complete responses. To be able to make progress in treating advanced ACC disease, adjuvant multicenter trials must be encouraged. When mitotane-based therapies are used, monitored drug levels are mandatory.
authors.affiliation: Department of Surgery, Sahlgrenska University Hospital, Göteborg University, S-413 45 Göteborg, Sweden. hakan.ahlman@surgery.gu.se
authors.forename: H
authors.initials: H
authors.lastname: Ahlman
authors.forename: A
authors.initials: A
authors.lastname: Khorram-Manesh
authors.forename: S
authors.initials: S
authors.lastname: Jansson
authors.forename: B
authors.initials: B
authors.lastname: Wängberg
authors.forename: O
authors.initials: O
authors.lastname: Nilsson
authors.forename: C E
authors.initials: CE
authors.lastname: Jacobsson
authors.forename: S
authors.initials: S
authors.lastname: Lindstedt
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000188:drug therapy*; D018268:Adrenocortical Carcinoma / Q000188:drug therapy*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002945:Cisplatin / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D005047:Etoposide / Q000627:therapeutic use; D006801:Humans; D008939:Mitotane / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D005047:Etoposide; D008939:Mitotane; D004317:Doxorubicin; D002945:Cisplatin