Leonard R C F, Williams S, Tulpule A, Levine A M, Oliveros S
Imperial College NHS Trust, Hammersmith Hospital, Du Cane Road, London W12 OHS, UK.
Breast. 2009 Aug;18(4):218-24. doi: 10.1016/j.breast.2009.05.004. Epub 2009 Aug 4.
Anthracyclines are valuable cytotoxic agents in cancer treatment. However, their usefulness is limited by cumulative dose-dependent cardiotoxicity that may manifest as life-threatening congestive heart failure. To avoid cardiotoxicity, the use of doxorubicin is typically capped at a safe cumulative dose. Liposomal formulations may reduce cardiac risks whilst maintaining anti-cancer efficacy. Efficacy and safety studies of non-pegylated liposomal doxorubicin (NPLD) in metastatic breast cancer (MBC) are reviewed, along with studies that examine efficacy and cardiac tolerability in combination with newer agents such as paclitaxel and trastuzumab. These show that cardiac safety of liposomal doxorubicin is similar to that of epirubicin in cumulative dose, but that the formulation, unlike epirubicin, has similar anti-cancer efficacy to doxorubicin at equimolar doses. Liposomal doxorubicin may have a better therapeutic index than non-liposomal anthracyclines. This justifies further studies in patients where cumulative cardiotoxicity is a concern, as does study of its use with other potentially cardiotoxic agents.
蒽环类药物是癌症治疗中重要的细胞毒性药物。然而,其应用受到累积剂量依赖性心脏毒性的限制,这种毒性可能表现为危及生命的充血性心力衰竭。为避免心脏毒性,多柔比星的使用通常限制在安全累积剂量以内。脂质体制剂在维持抗癌疗效的同时可降低心脏风险。本文综述了非聚乙二醇化脂质体多柔比星(NPLD)在转移性乳腺癌(MBC)中的疗效和安全性研究,以及其与紫杉醇和曲妥珠单抗等新型药物联合使用时的疗效和心脏耐受性研究。这些研究表明,脂质体多柔比星的心脏安全性在累积剂量方面与表柔比星相似,但与表柔比星不同的是,该制剂在等摩尔剂量下与多柔比星具有相似的抗癌疗效。脂质体多柔比星可能比非脂质体蒽环类药物具有更好的治疗指数。这为在关注累积心脏毒性的患者中开展进一步研究提供了依据,同时也为研究其与其他潜在心脏毒性药物联合使用提供了依据。