L Ghataore
L Ghataore
Departments of, Clinical Biochemistry, Medicine, Department of Endocrinology and Internal Medicine, King's College Hospital, London SE5 9RS, UK
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I Chakraborti
I Chakraborti
Departments of, Clinical Biochemistry, Medicine, Department of Endocrinology and Internal Medicine, King's College Hospital, London SE5 9RS, UK
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S J Aylwin
S J Aylwin
Departments of, Clinical Biochemistry, Medicine, Department of Endocrinology and Internal Medicine, King's College Hospital, London SE5 9RS, UK
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K-M Schulte
K-M Schulte
Departments of, Clinical Biochemistry, Medicine, Department of Endocrinology and Internal Medicine, King's College Hospital, London SE5 9RS, UK
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D Dworakowska
D Dworakowska
Departments of, Clinical Biochemistry, Medicine, Department of Endocrinology and Internal Medicine, King's College Hospital, London SE5 9RS, UK
Departments of, Clinical Biochemistry, Medicine, Department of Endocrinology and Internal Medicine, King's College Hospital, London SE5 9RS, UK
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Departments of, Clinical Biochemistry, Medicine, Department of Endocrinology and Internal Medicine, King's College Hospital, London SE5 9RS, UK
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P Coskeran
P Coskeran
Departments of, Clinical Biochemistry, Medicine, Department of Endocrinology and Internal Medicine, King's College Hospital, London SE5 9RS, UK
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N F Taylor
N F Taylor
Departments of, Clinical Biochemistry, Medicine, Department of Endocrinology and Internal Medicine, King's College Hospital, London SE5 9RS, UK
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Introduction Mitotane (o,p'-DDD) plays an important role in adjuvant therapy of adrenocortical carcinoma (ACC) and in advanced stage disease (1) . This application was first reported in 1959 by Bergenstal et al . (2) , but mitotane has only been
Magdalena Lech
Magdalena Lech
Faculty of Life Sciences and Medicine, School of Life Course Sciences, King’s College London, London, UK
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Ruvini Ranasinghe
Ruvini Ranasinghe
Department of Clinical Biochemistry, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK
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Royce P Vincent
Royce P Vincent
Department of Clinical Biochemistry, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK
Faculty of Life Sciences and Medicine, School of Life Course Sciences, King’s College London, London, UK
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Faculty of Life Sciences and Medicine, School of Life Course Sciences, King’s College London, London, UK
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David R Taylor
David R Taylor
Department of Clinical Biochemistry, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK
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Lea Ghataore
Lea Ghataore
Department of Clinical Biochemistry, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK
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James Luxton
James Luxton
Department of Clinical Biochemistry, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK
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Fannie Lajeunesse-Trempe
Fannie Lajeunesse-Trempe
Department of Endocrinology ASO/EASO COM, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UK
Quebec Heart and Lung Institute, Laval University, Quebec, Canada
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Quebec Heart and Lung Institute, Laval University, Quebec, Canada
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Pia Roser
Pia Roser
Department of Endocrinology and Diabetes, University Medical Centre Hamburg Eppendorf, Hamburg, Germany
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Eftychia E Drakou
Eftychia E Drakou
Department of Clinical Oncology, Guy's Cancer Centre - Guy's and St Thomas' NHS Foundation Trust, Great Maze Pond, London, UK
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Ling Ling Chuah
Ling Ling Chuah
Department of Endocrinology ASO/EASO COM, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UK
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Ashley B Grossman
Ashley B Grossman
Green Templeton College, University of Oxford, Oxford, UK
Barts and the London School of Medicine, Centre for Endocrinology, William Harvey Institute, London, UK
Neuroendocrine Tumour Unit, Royal Free Hospital, London, UK
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Barts and the London School of Medicine, Centre for Endocrinology, William Harvey Institute, London, UK
Neuroendocrine Tumour Unit, Royal Free Hospital, London, UK
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Simon J B Aylwin
Simon J B Aylwin
Department of Endocrinology ASO/EASO COM, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UK
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Georgios K Dimitriadis
Georgios K Dimitriadis
Department of Endocrinology ASO/EASO COM, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UK
Obesity, Type 2 Diabetes and Immunometabolism Research Group, School of Cardiovascular and Metabolic Medicine & Sciences, Faculty of Life Course Sciences, King’s College London, London, UK
Division of Reproductive Health, Warwick Medical School, University of Warwick, Coventry, UK
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Obesity, Type 2 Diabetes and Immunometabolism Research Group, School of Cardiovascular and Metabolic Medicine & Sciences, Faculty of Life Course Sciences, King’s College London, London, UK
Division of Reproductive Health, Warwick Medical School, University of Warwick, Coventry, UK
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minimising the risk of metastasis ( 4 ). Adjunctive therapy with mitotane or other systemic cytotoxic agents may be offered to those post-surgery to minimise the risk of recurrence and in those with inoperable disease and/or metastatic disease. Despite the
Anne Jouinot
Anne Jouinot
Department of Medical Oncology, Cochin Hospital, Paris Descartes University, CARPEM, AP-HP, Paris, France
Institut Cochin, INSERM U1016, CNRS UMR8104, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
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Institut Cochin, INSERM U1016, CNRS UMR8104, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
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Bernard Royer
Bernard Royer
CHU Besançon, Clinical Pharmacology and Toxicology Dpt, Besançon cedex, France
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Etienne Chatelut
Etienne Chatelut
Institut Claudius-Regaud, Université de Toulouse, INSERM, Centre de Recherches en Cancérologie de Toulouse, Toulouse, France
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Sotheara Moeung
Sotheara Moeung
Institut Claudius-Regaud, Université de Toulouse, INSERM, Centre de Recherches en Cancérologie de Toulouse, Toulouse, France
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Guillaume Assié
Guillaume Assié
Institut Cochin, INSERM U1016, CNRS UMR8104, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
Department of Endocrinology, Center for Rare Adrenal Diseases, Hôpital Cochin, Assistance Publique Hôpitaux de Paris, Paris, France
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Department of Endocrinology, Center for Rare Adrenal Diseases, Hôpital Cochin, Assistance Publique Hôpitaux de Paris, Paris, France
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Audrey Thomas-Schoemann
Audrey Thomas-Schoemann
Department of Pharmacy, Cochin Hospital, Paris Descartes University, AP-HP, Paris, France
Pharmacokinetics and Pharmacochemistry Unit, Cochin Hospital, Paris Descartes University, AP-HP, Paris, France
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Pharmacokinetics and Pharmacochemistry Unit, Cochin Hospital, Paris Descartes University, AP-HP, Paris, France
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Jérôme Bertherat
Jérôme Bertherat
Institut Cochin, INSERM U1016, CNRS UMR8104, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
Department of Endocrinology, Center for Rare Adrenal Diseases, Hôpital Cochin, Assistance Publique Hôpitaux de Paris, Paris, France
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Department of Endocrinology, Center for Rare Adrenal Diseases, Hôpital Cochin, Assistance Publique Hôpitaux de Paris, Paris, France
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François Goldwasser
François Goldwasser
Department of Medical Oncology, Cochin Hospital, Paris Descartes University, CARPEM, AP-HP, Paris, France
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Benoit Blanchet
Benoit Blanchet
Pharmacokinetics and Pharmacochemistry Unit, Cochin Hospital, Paris Descartes University, AP-HP, Paris, France
UMR8638 CNRS, Pharmacy UFR, University of Paris Descartes, PRES sorbonne Paris Cité, Paris, France
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UMR8638 CNRS, Pharmacy UFR, University of Paris Descartes, PRES sorbonne Paris Cité, Paris, France
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and the extreme rarity of the disease hampers the development of new drugs ( 2 ). The combination of mitotane and etoposide/doxorubicin/cisplatin (EDP) is now the standard treatment in advanced ACC ( 3 ). However, overall response rate (23%) and
Emmanuelle Motte
Emmanuelle Motte
UFR des Sciences de la Santé, Simone Veil, Université Versailles St-Quentin en Yvelines, Montigny le Bretonneux, France
Assistance Publique Hôpitaux de Paris (APHP), Department of Endocrinology and Diabetes for Children, Bicêtre Paris-Sud, Le Kremlin Bicêtre, France
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Assistance Publique Hôpitaux de Paris (APHP), Department of Endocrinology and Diabetes for Children, Bicêtre Paris-Sud, Le Kremlin Bicêtre, France
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Anya Rothenbuhler
Anya Rothenbuhler
Assistance Publique Hôpitaux de Paris (APHP), Department of Endocrinology and Diabetes for Children, Bicêtre Paris-Sud, Le Kremlin Bicêtre, France
APHP, Plateforme d’Expertise Maladies Rares Paris Sud, Bicêtre Paris Sud Hospital, Le Kremlin Bicêtre, France
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APHP, Plateforme d’Expertise Maladies Rares Paris Sud, Bicêtre Paris Sud Hospital, Le Kremlin Bicêtre, France
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Stephan Gaillard
Stephan Gaillard
Department of Neurosurgery, Foch Hospital, Suresnes, France
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Najiba Lahlou
Najiba Lahlou
APHP, Department of Hormonal Biology, Cochin Hospital, Paris, France
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Cécile Teinturier
Cécile Teinturier
Assistance Publique Hôpitaux de Paris (APHP), Department of Endocrinology and Diabetes for Children, Bicêtre Paris-Sud, Le Kremlin Bicêtre, France
APHP, Plateforme d’Expertise Maladies Rares Paris Sud, Bicêtre Paris Sud Hospital, Le Kremlin Bicêtre, France
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APHP, Plateforme d’Expertise Maladies Rares Paris Sud, Bicêtre Paris Sud Hospital, Le Kremlin Bicêtre, France
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Régis Coutant
Régis Coutant
Department of Pediatric Endocrinology, Angers University Hospital, Angers, France
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Agnès Linglart
Agnès Linglart
Assistance Publique Hôpitaux de Paris (APHP), Department of Endocrinology and Diabetes for Children, Bicêtre Paris-Sud, Le Kremlin Bicêtre, France
APHP, Plateforme d’Expertise Maladies Rares Paris Sud, Bicêtre Paris Sud Hospital, Le Kremlin Bicêtre, France
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APHP, Plateforme d’Expertise Maladies Rares Paris Sud, Bicêtre Paris Sud Hospital, Le Kremlin Bicêtre, France
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, 15 , 16 ), prompting physicians to use alternative therapies such as pituitary radiotherapy or adrenolytic agents. O,p’-dichlorodiphenyldichloroethane (mitotane, Lysodren 500 mg; HRA Pharma, Paris, France) is an adrenolytic drug with a direct
Eric Seidel
Eric Seidel
Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Nephrology and Medical Intensive Care, BCRT – Berlin Institute of Health Center for Regenerative Therapies, Berlin, Germany
Berlin Institute of Health (BIH), Berlin, Germany
Department of Nephrology, School of Medicine, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany
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Berlin Institute of Health (BIH), Berlin, Germany
Department of Nephrology, School of Medicine, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany
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Gudrun Walenda
Gudrun Walenda
Department of Nephrology, School of Medicine, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany
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Clemens Messerschmidt
Clemens Messerschmidt
Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
Core Unit Bioinformatics, Berlin Institute of Health, Berlin, Germany
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Core Unit Bioinformatics, Berlin Institute of Health, Berlin, Germany
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Benedikt Obermayer
Benedikt Obermayer
Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
Core Unit Bioinformatics, Berlin Institute of Health, Berlin, Germany
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Core Unit Bioinformatics, Berlin Institute of Health, Berlin, Germany
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Mirko Peitzsch
Mirko Peitzsch
Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
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Paal Wallace
Paal Wallace
Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
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Rohini Bahethi
Rohini Bahethi
Department of Nephrology, School of Medicine, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany
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Taekyeong Yoo
Taekyeong Yoo
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea
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Murim Choi
Murim Choi
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea
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Petra Schrade
Petra Schrade
Charité – Universitaetsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institut für Vegetative Anatomie, Berlin, Germany
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Sebastian Bachmann
Sebastian Bachmann
Charité – Universitaetsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institut für Vegetative Anatomie, Berlin, Germany
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Gerhard Liebisch
Gerhard Liebisch
Institute of Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany
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Graeme Eisenhofer
Graeme Eisenhofer
Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
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Dieter Beule
Dieter Beule
Core Unit Bioinformatics, Berlin Institute of Health, Berlin, Germany
Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany
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Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany
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Ute I Scholl
Ute I Scholl
Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Nephrology and Medical Intensive Care, BCRT – Berlin Institute of Health Center for Regenerative Therapies, Berlin, Germany
Berlin Institute of Health (BIH), Berlin, Germany
Department of Nephrology, School of Medicine, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany
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Berlin Institute of Health (BIH), Berlin, Germany
Department of Nephrology, School of Medicine, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany
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treatment option for ACCs. Although the majority of patients have resectable disease at presentation, up to 85% relapse after radical resection ( 3 ), leading to an overall poor prognosis. Mitotane, a by-product of the industrial production of the
Deborah Cosentini
Deborah Cosentini
Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, ASST Spedali Civili, Brescia, Italy
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Salvatore Grisanti
Salvatore Grisanti
Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, ASST Spedali Civili, Brescia, Italy
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Alberto Dalla Volta
Alberto Dalla Volta
Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, ASST Spedali Civili, Brescia, Italy
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Marta Laganà
Marta Laganà
Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, ASST Spedali Civili, Brescia, Italy
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Chiara Fiorentini
Chiara Fiorentini
Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy
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Paola Perotti
Paola Perotti
Internal Medicine, Department of Clinical and Biological Sciences, San Luigi Hospital, University of Turin, Orbassano, Italy
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Sandra Sigala
Sandra Sigala
Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy
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Alfredo Berruti
Alfredo Berruti
Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, ASST Spedali Civili, Brescia, Italy
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mainstay of therapy. For patients with locally advanced or metastatic ACC, not amenable to surgery, mitotane and cytotoxic chemotherapy (with etoposide, doxorubicin and cisplatin – EDP scheme) are the systemic treatments currently in use ( 2 ). No
Maria Cristina De Martino
Maria Cristina De Martino
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
Dipartimento di Medicina Clinica e Chirurgia, Università Federico II, Naples, Italy
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Dipartimento di Medicina Clinica e Chirurgia, Università Federico II, Naples, Italy
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Richard A Feelders
Richard A Feelders
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
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Claudia Pivonello
Claudia Pivonello
Dipartimento di Medicina Clinica e Chirurgia, Università Federico II, Naples, Italy
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Chiara Simeoli
Chiara Simeoli
Dipartimento di Medicina Clinica e Chirurgia, Università Federico II, Naples, Italy
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Fortuna Papa
Fortuna Papa
Dipartimento di Medicina Clinica e Chirurgia, Università Federico II, Naples, Italy
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Annamaria Colao
Annamaria Colao
Dipartimento di Medicina Clinica e Chirurgia, Università Federico II, Naples, Italy
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Rosario Pivonello
Rosario Pivonello
Dipartimento di Medicina Clinica e Chirurgia, Università Federico II, Naples, Italy
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Leo J Hofland
Leo J Hofland
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
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6 days of treatment, the cells were harvested for DNA measurement In both H295 and SW13, the selected concentrations of sirolimus significantly inhibited cell proliferation Mitotane DNA measurement When mitotane was used at low concentrations
Jung Soo Lim
Jung Soo Lim
Department of Internal Medicine, Institute of Evidence-Based Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Gangwon-do, South Korea
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Seung-Eun Lee
Seung-Eun Lee
Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul, South Korea
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Jung Hee Kim
Jung Hee Kim
Department of Internal Medicine, Seoul National University College of Medicine, Jongno-gu, Seoul, South Korea
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Jae Hyeon Kim
Jae Hyeon Kim
Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul, South Korea
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The Korean Adrenal Gland and Endocrine Hypertension Study Group, Korean Endocrine Society
The Korean Adrenal Gland and Endocrine Hypertension Study Group, Korean Endocrine Society
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underwent surgery (84.1%), 149 of which were total adrenalectomy. Among 32 patients who did not undergo surgical treatment, 17 had identifiable data regarding one or more alternative palliative treatment methods: 5 for cytotoxic chemotherapy, 5 for mitotane
M S Elston
M S Elston
Department of Endocrinology, Waikato Hospital, Hamilton, New Zealand
Waikato Clinical Campus, University of Auckland, Hamilton, New Zealand
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Waikato Clinical Campus, University of Auckland, Hamilton, New Zealand
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V B Crawford
V B Crawford
Department of Endocrinology, Waikato Hospital, Hamilton, New Zealand
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M Swarbrick
M Swarbrick
Department of Radiology, Waikato Hospital, Hamilton, New Zealand
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M S Dray
M S Dray
Department of Pathology, Waikato Hospital, Hamilton, New Zealand
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M Head
M Head
Department of Oncology, Tauranga Hospital, Tauranga, New Zealand
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J V Conaglen
J V Conaglen
Waikato Clinical Campus, University of Auckland, Hamilton, New Zealand
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potential medical therapies to control hypercortisolism include mitotane, although the onset is slow, and mifepristone (not currently available in New Zealand) ( 10 ). Regular monitoring, both clinical and biochemical, is required to assess the efficacy of
Wenhao Lin
Wenhao Lin
Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Jun Dai
Jun Dai
Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Jialing Xie
Jialing Xie
Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Jiacheng Liu
Jiacheng Liu
Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Fukang Sun
Fukang Sun
Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Xin Huang
Xin Huang
Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Wei He
Wei He
Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Chen Fang
Chen Fang
Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Juping Zhao
Juping Zhao
Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Danfeng Xu
Danfeng Xu
Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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). Currently, complete tumor resection is the only curative alternative for ACC, although retrospective studies ( 2 , 3 , 4 ) have revealed the potential of adjuvant therapy in improving the prognosis, such as mitotane. The 5-year and median overall survival
