ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 P24 | DOI: 10.1530/endoabs.63.P24

Management of adjuvant mitotane therapy for adrenocortical carcinoma: a survey in Italy

Soraya Puglisi1, Anna Calabrese1, Vittoria Basile1, Rosario Pivonello2, Filippo Ceccato3, Carla Scaroni3, Massimo Torlontano4, Salvatore Cannavò5, Giorgio Arnaldi6, Antonio Stigliano7, Pasqualino Malandrino8, Laura Saba1, Barbara Altieri9, Silvia Della Casa9, Paola Perotti1, Paola Berchialla10, Giuseppina De Filpo11, Letizia Canu11, Paola Loli12, Giuseppe Reimondo1 & Massimo Terzolo1


1Internal Medicine, Department of Clinical and Biological Sciences, San Luigi Gonzaga Hospital, University of Turin, Orbassano, Italy; 2Endocrinology Unit, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy; 3Endocrinology Unit, Department of Medicine DIMED, University-Hospital of Padua, Padua, Italy; 4Endocrinology Unit, Hospital ‘Casa Sollievo della Sofferenza’, IRCCS, San Giovanni Rotondo, Italy; 5Department of Human Pathology of Adulthood and Childhood ‘G. Barresi’, University of Messina, Messina, Italy; 6Division of Endocrinology, Department of Clinical and Molecular Sciences (DISCLIMO), Polytechnic University of Marche, Ancona, Italy; 7Endocrinology, Department of Clinical and Molecular Medicine, Sant’Andrea Hospital, Sapienza University of Rome, Rome, Italy; 8Endocrinology Division, Department of Clinical and Experimental Medicine, ARNAS Garibaldi, University of Catania, Catania, Italy; 9Division of Endocrinology and Metabolic Diseases, University-Hospital Gemelli, IRCSS, Catholic University of the Sacred Heart, Rome, Italy; 10Statistical Unit, Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy; 11Endocrinology Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy; 12Endocrinology, Hospital Niguarda Ca’ Granda, Milan, Italy.


Background and objective: Mitotane is widely used as post-operative adjuvant treatment of adrenocortical carcinoma. However, the management of therapy is largely empirical. Mitotane monitoring is recommended but we do not know what impact target concentrations do have on patient outcome. The aim of the study is to evaluate its use in expert Italian centers, analyzing data of Lysosafe Online® database.

Methods: Retrospective analysis of patients reported on the Lysosafe Online® database, treated with mitotane for ≥6 months and with >3 measurements of plasma mitotane levels during follow-up. Data are expressed as median and interquartile range.

Results: We identified 110 patients (F/M=67/43, aged 47, 35–58 years), treated with adjuvant mitotane for 47 (28–62) months with a maintainment dose of 2.0 (1.5–2.5) g/day. Adjuvant treatment was initiated after 1 (1–2) months from first surgery in 92.7% and discontinued permanently in 53.6% of cases, of which 61.0% for end of treatment and 8.5% for toxicity. Achievement of target mitotane levels required 8 (5–19) months. At multivariate analysis, Ki67 index (HR 2.71, 95% CI, 1.06–6.90; P=0.048) and time to the first target level (HR 1.35, 95% CI, 1.02–1.80; P=0.046) were predictive factors of recurrence. In a separate model considering only the first 3 years of treatment, peak mitotane concentration was associated with lower risk of recurrence (HR 0.56, 95% CI, 0.38–0.85; P=0.006).

Conclusions: In Italy, a low-dose regimen of adjuvant mitotane therapy is used that has the likely advantage of being rather well tolerated for long time with the drawback of a slow rise of mitotane levels to target. The study shows that monitoring of mitotane levels may have an impact on patient outcome.

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