Tahover Esther, Patil Yogita P, Gabizon Alberto A
Oncology Institute, Shaare Zedek Medical Center and Hebrew University, School of Medicine, Jerusalem, Israel.
Anticancer Drugs. 2015 Mar;26(3):241-58. doi: 10.1097/CAD.0000000000000182.
Anthracyclines are powerful anticancer agents and among the most important tools in the chemotherapy armamentarium of medical oncologists. They are approved for use in the treatment of a broad variety of solid and hematologic neoplasms. However, the usefulness of these agents, particularly doxorubicin, the most widely used anthracycline, is limited by considerable toxicity, especially damage to the cardiac muscle, which is cumulative and mostly irreversible, restricting extended use of this drug. In the last 30 years, extensive research with a variety of drug-delivery systems has attempted to overcome this limitation, with clinical success mostly confined to liposome formulations. Liposomal doxorubicin, and particularly pegylated liposomal doxorubicin, has shown significant pharmacologic advantages and an added clinical value over doxorubicin. Here, we review the mechanisms of action and toxicity of doxorubicin, and ways to reduce toxicity, with a focus on liposome-based drug-delivery systems.
蒽环类药物是强大的抗癌剂，也是医学肿瘤学家化疗药库中最重要的工具之一。它们被批准用于治疗多种实体瘤和血液系统肿瘤。然而，这些药物，尤其是使用最广泛的蒽环类药物阿霉素，其有效性受到相当大的毒性限制，特别是对心肌的损害，这种损害是累积性的且大多不可逆，从而限制了该药物的广泛使用。在过去30年中，对各种药物递送系统进行了广泛研究，试图克服这一限制，临床成功大多局限于脂质体制剂。脂质体阿霉素，尤其是聚乙二醇化脂质体阿霉素，已显示出相对于阿霉素具有显著的药理学优势和附加的临床价值。在此，我们综述阿霉素的作用机制和毒性，以及降低毒性的方法，重点是基于脂质体的药物递送系统。
