Mitotane Concentrations Influence Outcome in Patients with Advanced Adrenocortical Carcinoma

• Published in: Cancers 2020-03, Vol.12 (3), p.740
• Main Authors: Puglisi, Soraya, Calabrese, Anna, Basile, Vittoria, Ceccato, Filippo, Scaroni, Carla, Altieri, Barbara, Della Casa, Silvia, Loli, Paola, Pivonello, Rosario, De Martino, Maria Cristina, Canu, Letizia, Russo, Marco, Badalamenti, Giuseppe, Torlontano, Massimo, Stigliano, Antonio, Ferraù, Francesco, Arnaldi, Giorgio, Saba, Laura, Quirino, Alessandra, Perotti, Paola, Berchialla, Paola, Terzolo, Massimo
• Format: Article
• Language: English
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers12030740

Mitotane is the main option of treatment for advanced adrenocortical carcinoma (ACC). However, limited evidence is available regarding the impact of plasma mitotane levels on patient outcome. To address this question, we retrospectively analyzed patients with advanced ACC treated with mitotane for ≥3 months, with ≥3 measurements of plasma mitotane reported in the Lysosafe Online database (HRA Pharma, France), followed at 12 tertiary centers in Italy from 2005 to 2017. We identified 80 patients, initially treated with mitotane alone (56.2%) or plus chemotherapy (43.8%). The preference toward combination therapy was given to de novo stage IV ACC and younger patients. After the first line of treatment, 25% of valid cases experienced clinical benefit (14.5% objective response, 10.5% stabilization of disease) and 75% progression, without differences between the groups of treatment. Patients with progression had a lower time in the target range (TTR) of plasma mitotane and an unfavorable outcome. Death occurred in 76.2% of cases and multivariate analysis showed that clinical benefit after first treatment and longer TTR were favorable predictors of overall survival (OS). In conclusion, the present findings support the importance of mitotane monitoring and strengthen the concept of a therapeutic window for mitotane.