Maria Riedmeier, Sonir R R Antonini, Silvia Brandalise, Tatiana El Jaick B Costa, Camila M Daiggi, Bonald C de Figueiredo, Ronald R de Krijger, Karla Emília De Sá Rodrigues, Cheri Deal, Jaydira Del Rivero, Gernot Engstler, Martin Fassnacht, Gabriela C Fernandes Luiz Canali, Carlos A Fernandes Molina, Elmas Nazli Gonc, Melis Gültekin, Harm R Haak, Tulay Guran, Emile J Hendriks Allaird, Jan Idkowiak, Michaela Kuhlen, David Malkin, Jagdish Prasad Meena, Christina Pamporaki, Emilia Pinto, Soraya Puglisi, Raul C Ribeiro, Lester D R Thompson, Bilgehan Yalcin, Max Van Noesel, Verena Wiegering
{"title":"关于肾上腺皮质肿瘤儿科患者米托坦治疗的国际共识：适应症、治疗和不良反应管理。","authors":"Maria Riedmeier, Sonir R R Antonini, Silvia Brandalise, Tatiana El Jaick B Costa, Camila M Daiggi, Bonald C de Figueiredo, Ronald R de Krijger, Karla Emília De Sá Rodrigues, Cheri Deal, Jaydira Del Rivero, Gernot Engstler, Martin Fassnacht, Gabriela C Fernandes Luiz Canali, Carlos A Fernandes Molina, Elmas Nazli Gonc, Melis Gültekin, Harm R Haak, Tulay Guran, Emile J Hendriks Allaird, Jan Idkowiak, Michaela Kuhlen, David Malkin, Jagdish Prasad Meena, Christina Pamporaki, Emilia Pinto, Soraya Puglisi, Raul C Ribeiro, Lester D R Thompson, Bilgehan Yalcin, Max Van Noesel, Verena Wiegering","doi":"10.1093/ejendo/lvae038","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Mitotane is an important cornerstone in the treatment of pediatric adrenal cortical tumors (pACC), but experience with the drug in the pediatric age group is still limited and current practice is not guided by robust evidence. Therefore, we have compiled international consensus statements from pACC experts on mitotane indications, therapy, and management of adverse effects.</p><p><strong>Methods: </strong>A Delphi method with 3 rounds of questionnaires within the pACC expert consortium of the international network groups European Network for the Study of Adrenal Tumors pediatric working group (ENSAT-PACT) and International Consortium of pediatric adrenocortical tumors (ICPACT) was used to create 21 final consensus statements.</p><p><strong>Results: </strong>We divided the statements into 4 groups: environment, indications, therapy, and adverse effects. We reached a clear consensus for mitotane treatment for advanced pACC with stages III and IV and with incomplete resection/tumor spillage. For stage II patients, mitotane is not generally indicated. The timing of initiating mitotane therapy depends on the clinical condition of the patient and the setting of the planned therapy. We recommend a starting dose of 50 mg/kg/d (1500 mg/m²/d) which can be increased up to 4000 mg/m2/d. Blood levels should range between 14 and 20 mg/L. Duration of mitotane treatment depends on the clinical risk profile and tolerability. Mitotane treatment causes adrenal insufficiency in virtually all patients requiring glucocorticoid replacement shortly after beginning. As the spectrum of adverse effects of mitotane is wide-ranging and can be life-threatening, frequent clinical and neurological examinations (every 2-4 weeks), along with evaluation and assessment of laboratory values, are required.</p><p><strong>Conclusions: </strong>The Delphi method enabled us to propose an expert consensus statement, which may guide clinicians, further adapted by local norms and the individual patient setting. In order to generate evidence, well-constructed studies should be the focus of future efforts.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":null,"pages":null},"PeriodicalIF":5.3000,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"International consensus on mitotane treatment in pediatric patients with adrenal cortical tumors: indications, therapy, and management of adverse effects.\",\"authors\":\"Maria Riedmeier, Sonir R R Antonini, Silvia Brandalise, Tatiana El Jaick B Costa, Camila M Daiggi, Bonald C de Figueiredo, Ronald R de Krijger, Karla Emília De Sá Rodrigues, Cheri Deal, Jaydira Del Rivero, Gernot Engstler, Martin Fassnacht, Gabriela C Fernandes Luiz Canali, Carlos A Fernandes Molina, Elmas Nazli Gonc, Melis Gültekin, Harm R Haak, Tulay Guran, Emile J Hendriks Allaird, Jan Idkowiak, Michaela Kuhlen, David Malkin, Jagdish Prasad Meena, Christina Pamporaki, Emilia Pinto, Soraya Puglisi, Raul C Ribeiro, Lester D R Thompson, Bilgehan Yalcin, Max Van Noesel, Verena Wiegering\",\"doi\":\"10.1093/ejendo/lvae038\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>Mitotane is an important cornerstone in the treatment of pediatric adrenal cortical tumors (pACC), but experience with the drug in the pediatric age group is still limited and current practice is not guided by robust evidence. Therefore, we have compiled international consensus statements from pACC experts on mitotane indications, therapy, and management of adverse effects.</p><p><strong>Methods: </strong>A Delphi method with 3 rounds of questionnaires within the pACC expert consortium of the international network groups European Network for the Study of Adrenal Tumors pediatric working group (ENSAT-PACT) and International Consortium of pediatric adrenocortical tumors (ICPACT) was used to create 21 final consensus statements.</p><p><strong>Results: </strong>We divided the statements into 4 groups: environment, indications, therapy, and adverse effects. We reached a clear consensus for mitotane treatment for advanced pACC with stages III and IV and with incomplete resection/tumor spillage. For stage II patients, mitotane is not generally indicated. The timing of initiating mitotane therapy depends on the clinical condition of the patient and the setting of the planned therapy. We recommend a starting dose of 50 mg/kg/d (1500 mg/m²/d) which can be increased up to 4000 mg/m2/d. Blood levels should range between 14 and 20 mg/L. Duration of mitotane treatment depends on the clinical risk profile and tolerability. Mitotane treatment causes adrenal insufficiency in virtually all patients requiring glucocorticoid replacement shortly after beginning. As the spectrum of adverse effects of mitotane is wide-ranging and can be life-threatening, frequent clinical and neurological examinations (every 2-4 weeks), along with evaluation and assessment of laboratory values, are required.</p><p><strong>Conclusions: </strong>The Delphi method enabled us to propose an expert consensus statement, which may guide clinicians, further adapted by local norms and the individual patient setting. In order to generate evidence, well-constructed studies should be the focus of future efforts.</p>\",\"PeriodicalId\":11884,\"journal\":{\"name\":\"European Journal of Endocrinology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.3000,\"publicationDate\":\"2024-03-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Endocrinology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/ejendo/lvae038\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Endocrinology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/ejendo/lvae038","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
International consensus on mitotane treatment in pediatric patients with adrenal cortical tumors: indications, therapy, and management of adverse effects.
Objective: Mitotane is an important cornerstone in the treatment of pediatric adrenal cortical tumors (pACC), but experience with the drug in the pediatric age group is still limited and current practice is not guided by robust evidence. Therefore, we have compiled international consensus statements from pACC experts on mitotane indications, therapy, and management of adverse effects.
Methods: A Delphi method with 3 rounds of questionnaires within the pACC expert consortium of the international network groups European Network for the Study of Adrenal Tumors pediatric working group (ENSAT-PACT) and International Consortium of pediatric adrenocortical tumors (ICPACT) was used to create 21 final consensus statements.
Results: We divided the statements into 4 groups: environment, indications, therapy, and adverse effects. We reached a clear consensus for mitotane treatment for advanced pACC with stages III and IV and with incomplete resection/tumor spillage. For stage II patients, mitotane is not generally indicated. The timing of initiating mitotane therapy depends on the clinical condition of the patient and the setting of the planned therapy. We recommend a starting dose of 50 mg/kg/d (1500 mg/m²/d) which can be increased up to 4000 mg/m2/d. Blood levels should range between 14 and 20 mg/L. Duration of mitotane treatment depends on the clinical risk profile and tolerability. Mitotane treatment causes adrenal insufficiency in virtually all patients requiring glucocorticoid replacement shortly after beginning. As the spectrum of adverse effects of mitotane is wide-ranging and can be life-threatening, frequent clinical and neurological examinations (every 2-4 weeks), along with evaluation and assessment of laboratory values, are required.
Conclusions: The Delphi method enabled us to propose an expert consensus statement, which may guide clinicians, further adapted by local norms and the individual patient setting. In order to generate evidence, well-constructed studies should be the focus of future efforts.
期刊介绍：
European Journal of Endocrinology is the official journal of the European Society of Endocrinology. Its predecessor journal is Acta Endocrinologica.
The journal publishes high-quality original clinical and translational research papers and reviews in paediatric and adult endocrinology, as well as clinical practice guidelines, position statements and debates. Case reports will only be considered if they represent exceptional insights or advances in clinical endocrinology.
Topics covered include, but are not limited to, Adrenal and Steroid, Bone and Mineral Metabolism, Hormones and Cancer, Pituitary and Hypothalamus, Thyroid and Reproduction. In the field of Diabetes, Obesity and Metabolism we welcome manuscripts addressing endocrine mechanisms of disease and its complications, management of obesity/diabetes in the context of other endocrine conditions, or aspects of complex disease management. Reports may encompass natural history studies, mechanistic studies, or clinical trials.
Equal consideration is given to all manuscripts in English from any country.
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