O'Brien Mary E R
Royal Marsden Hospital, NHS Trust, Sutton, Surrey, UK. maryo'
Anticancer Drugs. 2008 Jan;19(1):1-7. doi: 10.1097/CAD.0b013e3282f14a00.
Anthracyclines and taxanes are among the most active substances used in the treatment of metastatic breast cancer (MBC). Their frequent use in the adjuvant setting and in cumulative toxicities including cardiotoxicity, however, often limit their use in MBC. The trend towards the use of adjuvant trastuzumab-containing regimens, which can also produce cardiotoxicity, adds further support to the need for effective agents with improved tolerability in the metastatic setting. Pegylated liposomal doxorubicin (PLD) can be an effective alternative to conventional anthracyclines for certain women with MBC. In phase III clinical trials, PLD was as effective as doxorubicin and produced significantly less cardiotoxicity in women with MBC. The incidences of myelotoxicity, nausea/vomiting, and alopecia were also lower with PLD, whereas hand-foot syndrome and stomatitis occurred more frequently. Phase II and III trials conducted in women with MBC support the use of PLD monotherapy in patients relapsing after adjuvant anthracycline-containing therapy, in heavily pretreated patients with taxane-refractory disease, in patients with cardiovascular risk factors (e.g. hypertension and mediastinal irradiation), in elderly patients, and in patients for whom specific acute doxorubicin toxicities, such as alopecia, are particularly worrying.
蒽环类药物和紫杉烷类药物是用于治疗转移性乳腺癌(MBC)的最具活性的物质之一。然而,它们在辅助治疗中的频繁使用以及包括心脏毒性在内的累积毒性,常常限制了它们在MBC治疗中的应用。使用含曲妥珠单抗的辅助治疗方案(该方案也可产生心脏毒性)的趋势,进一步支持了在转移性治疗中需要耐受性更好的有效药物。对于某些MBC女性患者,聚乙二醇化脂质体阿霉素(PLD)可能是传统蒽环类药物的有效替代品。在III期临床试验中,PLD对MBC女性患者的疗效与阿霉素相当,且心脏毒性显著更低。PLD导致的骨髓毒性、恶心/呕吐和脱发的发生率也更低,而手足综合征和口腔炎的发生频率更高。针对MBC女性患者开展的II期和III期试验支持在以下患者中使用PLD单药治疗:接受含蒽环类药物辅助治疗后复发的患者、接受过大量预处理的紫杉烷难治性疾病患者、有心血管危险因素(如高血压和纵隔放疗)的患者、老年患者,以及对阿霉素特定急性毒性(如脱发)特别担忧的患者。