Cytotoxic treatment of adrenocortical carcinoma

Adrenocortical carcinoma (ACC) is a rare, aggressive tumor that is often de tected in an advanced stage, Medical treatment with the adrenotoxic drug mi totane has been used for decades, but critical prospective trials on its ro le in residual disease or as an adjuvant agent after surgical resection are still lacking, The concept of a critical threshold plasma level of the dru g must be confirmed in controlled studies, Because individual responsivenes s 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 s ingle agents (e,g,, doxorubicin or cisplatin) have been disappointing, with low response rates (< 30%) and a short response duration. Part of this ref ractoriness may be explained by the fact that ACC tumors express the multid rug-resistance gene MDR-I, Chemotherapy with multiple agents has been teste d in smaller series and has resulted in significant side effects. The best results were achieved by the combination of etoposide, doxorubicin, and cis platin associated with mitotane, achieving a response rate of 54%, includin g individual complete responses. To be able to make progress in treating ad vanced ACC disease, adjuvant multicenter trials must be encouraged. When mi totane-based therapies are used, monitored drug levels are mandatory.