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World Journal of Surgery

, Volume 25, Issue 7, pp 927–933 | Cite as

Cytotoxic treatment of adrenocortical carcinoma

  • Håkan AhlmanEmail author
  • Amir Khorram-Manesh
  • Svante Jansson
  • Bo Wängberg
  • Ola Nilsson
  • Carl-Erik Jacobsson
  • Sven Lindstedt
World Progress In Surgery: Adrenal Tumors

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.

Keywords

Gossypol Suramin Adrenocortical Carcinoma Aminoglutethimide Mitotane 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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 (<30%) et une durée de réponse courte. Une partie de cette non-réonse peut être expliquée par le fait que les CCS expriment un gène de résistance multidrogues, le MDR-1. La plurichimiothérapie a été testée dans de plus petites séries avec des effets secondaires importants. Les meilleurs résultats ont été avec la combinaison d’étoposide, de doxorubicine et de cisplatine associés au mitotane: le taux de réponse a été de 54%, avec quelques réponses individuelles complètes. Pour faire des progrès dans le CCS avancé, il faut encourager des essais multicentriques de traitement adjuvant. En cas de thérapie utilisant le mitotane, il faut obligatoirement monitorer le taux des drogues.

Resumen

El carcinoma adrenocortical (CAC) es un tumor agresivo poco frecuente que comûnmente se détecta cuando ya esta en etapas avanzadas de su desarrollo. Desde hace décadas se practica tratamiento médico con una droga adrenotöxica, el mitotane, pero no se dispone de ensayos clînicos prospectivos que soporten su valor en enfermedad residual o como adyuvante de la resection quirürgica. También se hace necesario confirmar el concepto de nivelés criticos de la droga mediante estudios controlados. Puesto que no es posible predecir la respuesta individual, todavia se aconseja el uso del mitotane en casos de enfermedad no resecable. Cuando hay superproduction de Cortisol o de otros esteroides, se pueden utilizar algunas drogas como el Ketoconazol o la aminoglutetimida. La quimioterapia con agentes ûnicos, por ejemplo doxorubicina y el cisplatino, ha sido decepcionante, por las bajas tasas (<30%) y la corta duration de la respuesta. Parte de tal situation refractaria puede explicarse por el hecho de que los CAC expresan el gen MDR-1 de resistencia multidroga. La quimioterapia con agentes multiples ha sido ensayada en series mas pequenas, con efectos secundarios significatives. Los mejores resultados se logran con la combination de etopösido, doxorubicina y cisplatino asociada con mitotane, alcanzando una tasa de respuesta del 54%, incluyendo respuestas complétas. Para lograr progreso en el manejo del CAC avanzado se debe estimular la realization de ensayos multi-institucionales. La monitoria de los nivelés de droga son obligatorios cuando se usan terapias con base en mitotane.

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Copyright information

© Société Internationale de Chirurgie 2001

Authors and Affiliations

  • Håkan Ahlman
    • 1
    • 4
    Email author
  • Amir Khorram-Manesh
    • 1
    • 4
  • Svante Jansson
    • 1
    • 4
  • Bo Wängberg
    • 1
    • 4
  • Ola Nilsson
    • 2
    • 4
  • Carl-Erik Jacobsson
    • 3
  • Sven Lindstedt
    • 3
  1. 1.Department of SurgerySahlgrenska University Hospital, Göteborg UniversityGöteborgSweden
  2. 2.Department of PathologySahlgrenska University Hospital, Göteborg UniversityGöteborgSweden
  3. 3.Department of Clinical ChemistrySahlgrenska University Hospital, Göteborg UniversityGöteborgSweden
  4. 4.Lundberg Laboratory for Cancer ResearchSahlgrenska University Hospital, Göteborg UniversityGöteborgSweden

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