Cytotoxic treatment of adrenocortical carcinoma

• Published in: World journal of surgery 2001-07, Vol.25 (7), p.927-933
• Main Authors: Ahlman, Håkan, Khorram‐Manesh, Amir, Jansson, Svante, Wängberg, Bo, Nilsson, Ola, Jacobsson, Carl‐Erik, Lindstedt, Sven
• Format: Article
• Language: English
• Subjects: Adrenal Cortex Neoplasms; Adrenal Cortex Neoplasms - drug therapy; Adrenocortical Carcinoma; Adrenocortical Carcinoma - drug therapy; Aminoglutethimide; Antineoplastic Agents; Antineoplastic Agents - therapeutic use; Cancer; Chemotherapy; Cisplatin; Cisplatin - therapeutic use; Cortisol; Cytotoxicity; Doxorubicin; Doxorubicin - therapeutic use; Drug resistance; drug therapy; Etoposide; Etoposide - therapeutic use; Gossypol; Health services; Hormones; Humans; Hydrocortisone; Ketoconazole; Kirurgi; Medical treatment; Mitotane; Mitotane - therapeutic use; Neuroendocrine tumors; P-Glycoprotein; Side effects; Suramin; Surgery; therapeutic use; Thermal resistance; Tumors
• ISSN: 0364-2313; 1432-2323
• DOI: 10.1007/s00268-001-0031-6

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. Résumé Le cancer de la corticosurrénale (CCS) est une tumeur rare mais agressive, détectée souvent à un stade avancé. Le traitement médical par le mitotane, une drogue adrénotoxique, est utilisée depuis plusieurs décennies, mais, on manque d’essais prospectifs critiques sur son rôle dans la maladie résiduelle ou comme agent adjuvant après résection chirurgicale. Le concept d’un niveau plasmatique dont le seuil critique doit être confirmé par des études contrôlées. Puisqu’on ne peut prédire la réponse individuelle, le mitotane est toujours conseillé dans les maladies nonréséquables. En cas d’hyperproduction de Cortisol, ou d’autres Steroides, d’autres drogues, comme par exemple, le cétoconazole ou l’aminogluthétimide peuvent être utilisées. La monochimiothérapie, avec par exemple la doxorubicine et le cisplatine, est décevante avec un taux de réponse bas (