米托坦治疗肾上腺皮质癌专家共识(2021)

Consensus on the Treatment of Adrenocortical Carcinoma with Mitotane(2021)

肾上腺皮质癌(adrenocortical carcinoma,ACC)是发生于肾上腺皮质的罕见恶性肿瘤,手术为其首选治疗方式。对于无法手术切除、肿瘤已发生转移或术后有病灶残留的患者,药物治疗和放疗可作为辅助治疗方式。米托坦是美国食品药品监督管理局和欧洲药品管理局批准的适应证为ACC的唯一药物,其通过抑制线粒体呼吸、引起线粒体相关膜功能障碍及内质网应激等途径减少ACC细胞增殖,同时通过调控多种类固醇激素合成酶的功能和表达水平进而降低ACC细胞分泌功能,是多个国际指南和共识推荐的ACC首选辅助治疗药物。米托坦治疗期间需维持血药浓度在14~20 mg/L之间,监测药物相关不良反应,并警惕与其他药物的相互作用。为促进我国米托坦治疗ACC临床应用进一步规范化,保障用药的有效性和安全性,北京协和医院依托罕见病多学科诊疗团队,组织相关领域专家,经多次讨论、修改,最终制订了本共识,以供临床参考。

Adrenocortical carcinoma(ACC)is a rare malignant tumor that occurs in the adrenal cortex,and surgery is the first choice for treating ACC.Medical therapy and radiotherapy are adjuvant treatments for patients with unresectable metastasized tumors or incomplete resection.Mitotane is the only adrenergic cytotoxic drug approved by the American Food and Drug Administration and European Medicines Agency for the treatment of ACC by inhibiting mitochondrial respiration,causing mitochondrial membrane dysfunction and inducing endoplasmic reticulum stress,and it reduces the secretory function of ACC cells by inhibiting the function and expression of several enzymes in the adrenocortical steroidogenesis pathway.Mitotane is recommended as the first choice for adjuvant therapy by multiple international guidelines and consensus.During treatment with mitotane,its blood concentration should be maintained between 14 to 20 mg/L,while the related adverse drug reactions and drug-drug interactions should also be monitored.To promote further standardization of the clinical application of mitotane,and to ensure the effectiveness and safety of mitotane,Peking Union Medical College Hospital relied on the multi-disciplinary team for the diagnosis and treatment of rare diseases,organized experts and scholars in related fields to discuss and modify many times,and finally formed this consensus for clinicians’reference.