Mitotane Concentrations Influence the Risk of Recurrence in Adrenocortical Carcinoma Patients on Adjuvant Treatment

Journal of Clinical Medicine

Salvatore Cannavò¹  Barbara Altieri²  Silvia Della Casa²  Giorgio Arnaldi³  Pasqualino Malandrino⁴  Chiara Simeoli⁵  Giuseppina De Filpo⁶  Letizia Canu⁶  Filippo Ceccato⁷  Carla Scaroni⁷  Massimo Torlontano⁸  Antonio Stigliano⁹  Paola Loli^1,10  Laura Saba^1,11  Paola Perotti^1,11  Giuseppe Reimondo^1,11  Massimo Terzolo^1,11  Anna Calabrese^1,11  Soraya Puglisi^1,11  Vittoria Basile^1,11  Paola Berchialla^1,12 

[1] Department of Human Pathology of Adulthood and Childhood ‘G. Barresi’, University of Messina, 98125 Messina, Italy;Division of Endocrinology and Metabolic Diseases, University-Hospital Gemelli, IRCSS, Catholic University of the Sacred Heart, 00168 Rome, Italy;Division of Endocrinology, Department of Clinical and Molecular Sciences (DISCLIMO), Polytechnic University of Marche, 60121 Ancona, Italy;Endocrinology Division, Department of Clinical and Experimental Medicine, ARNAS Garibaldi, University of Catania, 95122 Catania, Italy;Endocrinology Unit, Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy;Endocrinology Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50134 Florence, Italy;Endocrinology Unit, Department of Medicine DIMED, University-Hospital of Padua, 35128 Padova, Italy;Endocrinology Unit, Hospital “Casa Sollievo della Sofferenza”, IRCCS, 71013 San Giovanni Rotondo, Italy;Endocrinology, Department of Clinical and Molecular Medicine, Sant’Andrea Hospital, Sapienza University of Rome, 00189 Roma, Italy;Endocrinology, Hospital Niguarda Ca’ Granda, 20121 Milan, Italy;Internal Medicine, Department of Clinical and Biological Sciences, San Luigi Gonzaga Hospital, University of Turin, 10043 Orbassano, Italy;Statistical Unit, Department of Clinical and Biological Sciences, University of Turin, 10143 Orbassano, Italy;

关键词: adrenocortical carcinoma;    mitotane;    prognosis;    recurrence;    survival;   

DOI  :  10.3390/jcm8111850

来源: DOAJ

【 摘 要 】

Mitotane is used as a post-operative adjuvant treatment for patients with adrenocortical carcinoma. Monitoring of plasma mitotane concentrations is recommended, but we do not know what impact target concentrations have on patient outcome. To answer this question, we retrospectively analyzed patient records in the Lysosafe Online^® database (HRA Pharma, France) for patients who were treated for ≥6 months and who had ≥3 measurements of plasma mitotane levels during follow-ups at 11 tertiary centers in Italy from 2005 to 2017. We identified 110 patients treated with adjuvant mitotane for a median of 46 months (IQR, interquartile range, 28−62) with a median maintenance dose of 2.0 g/day (IQR 1.5−2.5). Achievement of target mitotane concentrations (≥14 mg/L) required a median of 8 months (IQR 5−19). Female sex was associated inversely with the dose, while body mass index (BMI) was correlated positively. Multivariate analysis showed that the Ki67 index and time to achieve the target range of plasma mitotane were independent predictors of recurrence-free survival (RFS). In a separate multivariate model, considering only the maintenance phase (month 7 to month 36, M7−M36) of treatment, the time in the target range of plasma mitotane was associated with a significantly lower risk of recurrence (Hazard Ratio, HR = 0.93; 0.88−0.98, p < 0.01). The prognostic implications of the time in target range and the time needed to reach target mitotane concentrations support the use of mitotane monitoring and may inform practice.

【 授权许可】

Unknown