Endocrine Abstracts

JOINT3742

Mitotane is an adrenolytic drug used as adjuvant therapy in patients with adrenocortical carcinoma (ACC) at high risk of recurrence or as first-line treatment for unresectable tumors. Its antineoplastic efficacy correlates with plasma concentration, making the early achievement of the therapeutic threshold (14 mg/l) crucial. However, interindividual variability in mitotane pharmacokinetics poses challenges in reaching this target concentration within an optimal timeframe. This study aimed to identify factors influencing the time required to achieve therapeutic mitotane levels.

Methods: We retrospectively analyzed 51 patients with ACC aged 18 to 72 (median 54 years) ENSAT stage I–IV treated with mitotane for at least 6 months. In stage I there was 1 patient, stage II 17 patients, stage III 17 patients and in stage IV 16 patients. 34 patients recived mitotane monotherapy and 17 of them recived combination of mitotane with chemoterapy (EP or EDP protocol). In 82% of the patients we used high dose approach, and in 18% low dose approach of mitotane therapy. Mitotane concentrations were obtained from Lysosafe service which provides a centralized analysis of mitotane levels using high-performance liquid chromatography (HPLC).

Results: The median time to achieve the target plasma mitotane concentration was 89 days (30–300, IQR 49–129). There was no significant difference in the time required to reach the target mitotane concentration between patients treated with the high-dose and low-dose approaches (median 86 days (range 26–300 days) vs. 92.5 days (range 32–275 days), respectively). Similarly, the time to reach the target mitotane concentration was not influenced by age at diagnosis, body mass index, ENSAT stage, tumor size, or tumor hormonal activity. Although patients receiving mitotane in combination with chemotherapy reached the target concentration more slowly than those receiving mitotane monotherapy (median 113 days (range 32–174) vs. 85 days (range 32–300)), this difference was not statistically significant.

Conclusion: No clinical parameter was found to significantly impact the time required to achieve therapeutic mitotane levels. However, given the relatively small sample size, our study may have been underpowered to detect subtle differences. Larger, multicenter studies with a greater number of patients are needed to more comprehensively evaluate this issue.