Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital Würzburg, University of Würzburg, Würzburg, Germany.
Department of Diagnostic and Interventional Radiology, University Hospital Würzburg, University of Würzburg, Würzburg, Germany.
J Clin Endocrinol Metab. 2018 Apr 1;103(4):1686-1695. doi: 10.1210/jc.2017-02591.
Although mitotane is the only approved drug for the treatment of adrenocortical carcinoma (ACC), data on monotherapy in advanced disease are still scarce.
To assess the efficacy of mitotane in advanced ACC in a contemporary setting and to identify predictive factors.
Multicenter cohort study of three German referral centers.
One hundred twenty-seven patients with advanced ACC treated with mitotane monotherapy.
Response Evaluation Criteria in Solid Tumors evaluation, progression-free survival (PFS) and overall survival (OS) by Kaplan-Meier method, and predictive factors by Cox regression.
Twenty-six patients (20.5%) experienced objective response, including three with complete remission. Overall, median PFS was 4.1 months (range 1.0 to 73) and median OS 18.5 months (range 1.3 to 220). Multivariate analysis indicated two main predictive factors: low tumor burden (<10 tumoral lesions), hazard ratio (HR) for progression of 0.51 (P = 0.002) and for death of 0.59 (P = 0.017); and initiation of mitotane at delayed advanced recurrence, HR 0.35(P < 0.001) and 0.34 (P < 0.001), respectively. Accordingly, 67% of patients with low tumor burden and mitotane initiation ≥360 days after primary diagnosis experienced a clinical benefit (stable disease >180 days). Patients who achieved mitotane levels >14 mg/L had significantly longer OS (HR 0.42; P = 0.003).
At 20.5% the objective response rate was slightly lower than previously reported. However, >20% of patients experienced long-term disease control at >1 year. In general, patients with late diagnosis of advanced disease and low tumor burden might especially benefit from mitotane monotherapy, whereas patients with early advanced disease and high tumor burden are probably better candidates for combined therapy of mitotane and cytotoxic drugs.
虽然米托坦是治疗肾上腺皮质癌（ACC）的唯一批准药物，但关于晚期疾病的单药治疗数据仍然很少。
评估米托坦在当代晚期 ACC 中的疗效，并确定预测因素。
来自三个德国转诊中心的多中心队列研究。
127 例接受米托坦单药治疗的晚期 ACC 患者。
实体瘤反应评价标准（RECIST）评估、无进展生存期（PFS）和总生存期（OS）的 Kaplan-Meier 方法，以及 Cox 回归分析的预测因素。
26 例（20.5%）患者出现客观反应，包括 3 例完全缓解。总体而言，中位 PFS 为 4.1 个月（范围 1.0 至 73），中位 OS 为 18.5 个月（范围 1.3 至 220）。多变量分析表明有两个主要的预测因素：肿瘤负荷低（<10 个肿瘤病变），进展风险比（HR）为 0.51（P = 0.002），死亡风险比（HR）为 0.59（P = 0.017）；以及延迟的晚期复发后开始使用米托坦，HR 分别为 0.35（P < 0.001）和 0.34（P < 0.001）。相应地，67%的肿瘤负荷低且米托坦起始治疗时间≥360 天后的患者出现临床获益（稳定疾病持续时间>180 天）。米托坦水平>14 mg/L 的患者 OS 显著延长（HR 0.42；P = 0.003）。
客观缓解率为 20.5%，略低于既往报道。然而，>20%的患者在>1 年内疾病得到长期控制。总体而言，晚期疾病诊断延迟且肿瘤负荷低的患者可能特别受益于米托坦单药治疗，而早期晚期疾病且肿瘤负荷高的患者可能更适合米托坦联合细胞毒药物的联合治疗。
Zotero 插件