Marlene and Stewart Greenebaum Cancer Center, University of Maryland, Baltimore, Maryland 21201, USA.
Clin Ther. 2009;31 Pt 2:2273-89. doi: 10.1016/j.clinthera.2009.11.011.
Treatment of metastatic breast cancer (MBC) with > or =2 chemotherapeutic agents concurrently has been shown to increase response rates, often at the cost of a substantial increase in toxicity, and with minimal impact on the overall survival. However, some combinations of the newer cytotoxic agents, as well as combinations of chemotherapeutic agents and targeted biologic anticancer agents, can produce synergistic efficacy with a manageable toxicity profile.
The aims of this work were to provide an overview of the currently approved combination regimens available for the treatment of MBC and to consider the clinical data supporting other drug combinations that may supplement the current therapeutic choices in the near future.
Literature searches were performed using MEDLINE/PubMed, with a focus on combination therapies for the treatment of MBC that are approved by the US Food and Drug Administration (FDA) or in Phase III clinical trials. The National Institutes of Health's Clinical Trial Registry was searched for relevant ongoing clinical trials in specific areas. Bibliographies were also searched for additional relevant material. Preference was given to recently published, larger, well-designed clinical trials that influence current prescribing practices. Phase I and II studies, and/or studies older than 10 years (ie, published earlier than 1999), were afforded less emphasis or were disregarded.
Combinations of taxanes with capecitabine or gemcitabine, and ixabepilone plus capecitabine, are approved by the FDA as combination regimens for the treatment of MBC. The use of targeted therapies such as trastuzumab, bevacizumab, or lapatinib in combination with taxanes (for the former two) or capecitabine (for lapatinib) is also approved. Several investigational drug combinations are also currently undergoing evaluation in clinical trials, including combinations of bevacizumab and gemcitabine with capecitabine or alternative taxanes. Although results from Phase I and II studies are largely encouraging so far, the data from ongoing Phase III studies will ultimately dictate changes in clinical practice. It seems unlikely that any single agent or combination regimen will emerge as superior in all patients with MBC, given the heterogeneous nature of the disease and patient population.
New combination regimens for MBC may broaden the range of treatment options currently available to delay disease progression for as long as possible.
同时使用 > 或 =2 种化疗药物治疗转移性乳腺癌 (MBC) 已被证明可以提高缓解率，尽管这通常会导致毒性显著增加，但对总生存期的影响极小。然而，一些新型细胞毒性药物的组合，以及化疗药物和靶向生物抗癌药物的组合，可以产生协同疗效，同时具有可管理的毒性特征。
本工作旨在提供目前批准的用于治疗 MBC 的联合治疗方案概述，并考虑支持其他药物组合的临床数据，这些药物组合可能在不久的将来补充当前的治疗选择。
使用 MEDLINE/PubMed 进行文献检索，重点关注已被美国食品和药物管理局 (FDA) 批准或正在进行 III 期临床试验的用于治疗 MBC 的联合治疗。在特定领域，还在国家卫生研究院的临床试验注册处搜索相关的正在进行的临床试验。也对参考文献进行了搜索，以寻找其他相关资料。优先考虑最近发表的、更大规模的、设计良好的临床试验，这些试验影响当前的处方实践。对 I 期和 II 期研究，以及/或 10 年以上的研究（即发表于 1999 年之前），给予的重视较少或被忽略。
FDA 批准了紫杉醇与卡培他滨或吉西他滨，以及伊沙匹隆与卡培他滨联合作为治疗 MBC 的联合治疗方案。曲妥珠单抗、贝伐单抗或拉帕替尼等靶向治疗药物与紫杉醇（前两者）或卡培他滨（拉帕替尼）联合使用也已获得批准。目前，一些研究性药物组合也正在临床试验中进行评估，包括贝伐单抗和吉西他滨联合卡培他滨或替代紫杉醇的组合。尽管到目前为止，I 期和 II 期研究的结果大多令人鼓舞，但正在进行的 III 期研究的数据最终将决定临床实践的改变。考虑到疾病和患者群体的异质性，似乎不太可能有一种单一的药物或联合治疗方案在所有 MBC 患者中都表现出优越性。
MBC 的新联合治疗方案可能会扩大当前可用的治疗选择范围，尽可能长时间地延缓疾病进展。
