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Alessandra Mangone, Barbara Altieri, Mario Detomas, Alessandro Prete, Haider Abbas, Miriam Asia, Yasir S Elhassan, Giovanna Mantovani, and Cristina L Ronchi

tumour burden and/or slower growth rate, or in combination with etoposide, doxorubicin, and cisplatin (EDP) chemotherapy ( Fassnacht et al. 2018 , Fassnacht et al. 2020 ). Nevertheless, mitotane with or without EDP is associated with a relatively

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Sara Jung, Zoltan Nagy, Martin Fassnacht, Gerard Zambetti, Max Weiss, Martin Reincke, Peter Igaz, Felix Beuschlein, and Constanze Hantel

is mainly restricted to common cytotoxic agents ( Berruti et al . 2012 , Kroiss et al . 2012 , Fassnacht et al . 2015 ). The current mainstay of treatment for advanced and metastasized ACC is defined as the EDP-M protocol ( Fassnacht et al

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Elisa Roca, Alfredo Berruti, Silviu Sbiera, Ida Rapa, Ester Oneda, Paola Sperone, Cristina L Ronchi, Laura Ferrari, Salvatore Grisanti, Antonina Germano, Barbara Zaggia, Giorgio Vittorio Scagliotti, Martin Fassnacht, Marco Volante, Massimo Terzolo, and Mauro Papotti

multinational prospective randomized clinical study have established the combination chemotherapy with the topoisomerase II inhibitor etoposide, anthracycline, doxorubicin, cisplatin plus mitotane (EDP-M) as the reference regimen for this rare disease

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Constanze Hantel, Sara Jung, Thomas Mussack, Martin Reincke, and Felix Beuschlein

: streptozotocin plus mitotane (Sz-M) vs etoposide, doxorubicin, and cisplatin plus mitotane (EDP-M) ( Fassnacht et al . 2012 ). Within this study design, EDP-M resulted in higher response rates and longer progression-free survival in comparison with Sz

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Alfredo Berruti, Massimo Terzolo, Paola Sperone, Anna Pia, Silvia Della Casa, David J Gross, Carlo Carnaghi, Paolo Casali, Francesco Porpiglia, Franco Mantero, Giuseppe Reimondo, Alberto Angeli, and Luigi Dogliotti

intracellular drug accumulation and enhancing drug cytotoxicity ( Bates et al. 1991 , Villa et al. 1999 ). Since 1993, a multicenter phase II trial started in Italy with the aim of testing the activity of mitotane administered in association to EDP

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Paola Sperone, Anna Ferrero, Fulvia Daffara, Adriano Priola, Barbara Zaggia, Marco Volante, Daniele Santini, Bruno Vincenzi, Giuseppe Badalamenti, Chiara Intrivici, Sabrina Del Buono, Silvia De Francia, Emmanouil Kalomirakis, Riccardo Ratti, Alberto Angeli, Luigi Dogliotti, Mauro Papotti, Massimo Terzolo, and Alfredo Berruti

more efficacious than non-cisplatin-containing ones is being addressed by a large multicenter, multinational, randomized prospective study that is currently ongoing with the aim to compare efficacy of etoposide, doxorubicin, and cisplatin (EDP) plus

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Andrea Abate, Mariangela Tamburello, Elisa Rossini, Ram Manohar Basnet, Giovanni Ribaudo, Alessandra Gianoncelli, Constanze Hantel, Deborah Cosentini, Marta Laganà, Salvatore Grisanti, Guido Alberto Massimo Tiberio, Maurizio Memo, Alfredo Berruti, and Sandra Sigala

chemotherapeutic drugs etoposide (E), doxorubicin (D), and cisplatin (C) in advanced/metastatic ACC patients is not eligible for surgery ( Berruti et al. 2005 , Fassnacht et al. 2020 ). The EDP-mitotane (EDP-M) approach, however, has limited efficacy with

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B Wängberg, A Khorram-Manesh, S Jansson, B Nilsson, O Nilsson, C E Jakobsson, S Lindstedt, A Odén, and H Ahlman

and cisplatin (EDP-regimen) versus streptozotocin is currently under investigation for palliative purposes in the FIRM-ACT study ( ). The prognosis in ACC relates to tumour stage ( Icard et al . 2001 , Abiven et al

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T M A Kerkhofs, M H T Ettaieb, I G C Hermsen, and H R Haak

resection; R1, microscopic residual tumour; R2, macroscopic residual tumour; Rx, resection status undetermined; EDP, etoposide/doxorubicin/cisplatin; ADIUVO, Clinical trial testing efficacy of adjuvant mitotane treatment in prolonging recurrence

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Cristina L Ronchi, Silviu Sbiera, Luitgard Kraus, Sebastian Wortmann, Sarah Johanssen, Patrick Adam, Holger S Willenberg, Stefanie Hahner, Bruno Allolio, and Martin Fassnacht

and cisplatin (EDP) in the largest published trial including 72 patients with an objective response rate of 49%. However, this regimen has significant toxicity. Therefore, the determination of parameters that identify patients who will benefit from