Puglisi Soraya, Calabrese Anna, Basile Vittoria, Ceccato Filippo, Scaroni Carla, Simeoli Chiara, Torlontano Massimo, Cannavò Salvatore, Arnaldi Giorgio, Stigliano Antonio, Malandrino Pasqualino, Saba Laura, Altieri Barbara, Della Casa Silvia, Perotti Paola, Berchialla Paola, De Filpo Giuseppina, Canu Letizia, Loli Paola, Reimondo Giuseppe, Terzolo Massimo
Internal Medicine, Department of Clinical and Biological Sciences, San Luigi Gonzaga Hospital, University of Turin, 10043 Orbassano, Italy.
Endocrinology Unit, Department of Medicine DIMED, University-Hospital of Padua, 35128 Padova, Italy.
J Clin Med. 2019 Nov 2;8(11):1850. doi: 10.3390/jcm8111850.
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, < 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.
米托坦用作肾上腺皮质癌患者的术后辅助治疗。建议监测血浆米托坦浓度，但我们尚不清楚目标浓度对患者预后有何影响。为回答这个问题，我们回顾性分析了Lysosafe在线数据库（法国HRA制药公司）中2005年至2017年期间在意大利11个三级中心接受治疗≥6个月且在随访期间有≥3次血浆米托坦水平测量值的患者记录。我们确定了110例接受米托坦辅助治疗的患者，中位治疗时间为46个月（四分位间距IQR，28 - 62），中位维持剂量为2.0 g/天（IQR 1.5 - 2.5）。达到米托坦目标浓度（≥14 mg/L）中位需要8个月（IQR 5 - 19）。女性与剂量呈负相关，而体重指数（BMI）呈正相关。多变量分析显示，Ki67指数和达到血浆米托坦目标范围的时间是无复发生存期（RFS）的独立预测因素。在一个单独的多变量模型中，仅考虑治疗的维持阶段（第7个月至第36个月，M7 - M36），血浆米托坦处于目标范围内的时间与复发风险显著降低相关（风险比，HR = 0.93；0.88 - 0.98，<0.01）。目标范围内时间和达到米托坦目标浓度所需时间的预后意义支持米托坦监测的应用，并可能为临床实践提供参考。
