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, 3558 years), treated with adjuvant mitotane for 47 (2862) months with a maintainment dose of 2.0 (1.52.5) g/day. Adjuvant treatment was initiated after 1 (12) 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 (519) months. At multivariate analysis, Ki67 index (HR 2.71, 95% CI, 1.066.90; P=0.048) and time to the first target level (HR 1.35, 95% CI, 1.021.80; 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, 0.380.85; 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.
18 - 21 May 2019
European Society of Endocrinology