Franco Yesenia L, Vaidya Tanaya R, Ait-Oudhia Sihem
Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, FL, USA,
Breast Cancer (Dove Med Press). 2018 Sep 11;10:131-141. doi: 10.2147/BCTT.S170239. eCollection 2018.
Breast cancer (BC) is a highly prevalent disease, accounting for the second highest number of cancer-related mortalities worldwide. The anthracycline doxorubicin (DOX), isolated from var. , is a potent chemotherapeutic drug that is successfully used to treat various forms of liquid and solid tumors and is currently approved to treat BC. DOX exerts its effects by intercalation into DNA and inhibition of topoisomerases I and II, causing damage to DNA and the formation of reactive oxygen species (ROS), resulting in the activation of caspases, which ultimately leads to apoptosis. Unfortunately, DOX also can cause cardiotoxicity, with patients only allowed a cumulative lifetime dose of 550 mg/m. Efforts to decrease cardiotoxicity and to increase the blood circulation time of DOX led to the US Food and Drug Administration (FDA) approval of a PEGylated liposomal formulation (L-DOX), Doxil (known internationally as Caelyx). Both exhibit better cardiovascular safety profiles; however, they are not currently FDA approved for the treatment of metastatic BC. Here, we provide detailed insights into the mechanism of action of L-DOX and its most common side effects and highlight results of its use in clinical trials for the treatment of BC as single agent and in combination with other commonly used chemotherapeutics.
乳腺癌（BC）是一种高度流行的疾病，在全球癌症相关死亡人数中占第二高。从变种下分离出的蒽环类药物阿霉素（DOX）是一种有效的化疗药物，已成功用于治疗各种形式的液体和实体肿瘤，目前被批准用于治疗乳腺癌。DOX通过嵌入DNA并抑制拓扑异构酶I和II发挥作用，导致DNA损伤和活性氧（ROS）的形成，从而激活半胱天冬酶，最终导致细胞凋亡。不幸的是，DOX也会引起心脏毒性，患者终身累积剂量仅允许550mg/m。为降低心脏毒性并延长DOX的血液循环时间所做的努力，促使美国食品药品监督管理局（FDA）批准了一种聚乙二醇化脂质体制剂（L-DOX），即多柔比星脂质体（国际上称为凯素）。两者都表现出更好的心血管安全性；然而，它们目前尚未获得FDA批准用于治疗转移性乳腺癌。在此，我们详细阐述了L-DOX的作用机制及其最常见的副作用，并重点介绍了其作为单一药物以及与其他常用化疗药物联合用于治疗乳腺癌的临床试验结果。
