Department of Pharmacy Practice, Albany College of Pharmacy and Health Sciences, Vermont Campus, Colchester, VT 05404, USA.
Am J Health Syst Pharm. 2009 Dec 1;66(23 Suppl 6):S3-8. doi: 10.2146/ajhp090438.
To review the role of combination therapy in the treatment of metastatic breast cancer and to describe strategies to help manage adverse events associated with combination therapy.
Although the median survival of patients with metastatic breast cancer has increased over the last several decades, new treatment options are needed to further improve survival and quality of life for these patients. Novel cytotoxic and noncytotoxic agents have recently been evaluated in combination regimens for patients with metastatic breast cancer. Combinations for metastatic breast cancer that appear in recently approved labeling include ixabepilone with capecitabine, and the targeted biological agent lapatinib in combination with capecitabine. Ixabepilone is the first of a new family of cytotoxic agents--the epothilones--to enter clinical practice. Similar to the taxanes, ixabepilone binds to and stabilizes intracellular microtubules, resulting in decreased DNA replication and cell proliferation. Ixabepilone possesses antitumor activity in taxane-resistant tumor cells and has been shown to significantly improve progression-free survival when used in combination with capecitabine in patients with taxane-resistant tumors. Lapatinib, an oral small-molecule inhibitor of human epidermal growth factor receptors-1 and -2, has been shown, when combined with capecitabine, to improve progression-free survival in patients with advanced metastatic breast cancer who had progressed on prior therapy. The combination of paclitaxel and bevacizumab carries approved labeling for treatment of metastatic breast cancer, although there are concerns about bevacizumab and the risk of toxicity.
Ongoing clinical trials continue to define the role of novel antitumor agents in combination regimens for patients with metastatic breast cancer. Targeted agents are less likely to produce adverse events that are typical of cytotoxic chemotherapy but, because of their effects on specific molecular targets, may cause toxicities that were previously uncommon in cancer therapy.
回顾联合治疗在转移性乳腺癌治疗中的作用，并描述有助于处理联合治疗相关不良事件的策略。
尽管过去几十年间转移性乳腺癌患者的中位生存期有所延长，但仍需要新的治疗方案来进一步提高这些患者的生存率和生活质量。最近评估了新型细胞毒性和非细胞毒性药物联合用于转移性乳腺癌患者的方案。最近批准的标签中包含用于转移性乳腺癌的联合方案，包括伊沙匹隆联合卡培他滨，以及靶向生物制剂拉帕替尼联合卡培他滨。伊沙匹隆是第一个进入临床实践的新型细胞毒性药物——埃坡霉素类药物家族的成员。与紫杉烷类药物相似，伊沙匹隆与细胞内微管结合并稳定其结构，从而减少 DNA 复制和细胞增殖。伊沙匹隆在紫杉烷耐药肿瘤细胞中具有抗肿瘤活性，并且在紫杉烷耐药肿瘤患者中与卡培他滨联合使用时已显示可显著改善无进展生存期。拉帕替尼是一种人表皮生长因子受体 1 和 2 的口服小分子抑制剂，当与卡培他滨联合使用时，已显示可改善先前治疗进展的晚期转移性乳腺癌患者的无进展生存期。紫杉醇联合贝伐单抗联合治疗转移性乳腺癌具有批准的适应证，尽管存在贝伐单抗相关毒性风险的担忧。
正在进行的临床试验继续确定新型抗肿瘤药物在转移性乳腺癌联合治疗方案中的作用。靶向药物不太可能产生典型细胞毒性化疗的不良事件，但由于其对特定分子靶点的作用，可能会引起以前在癌症治疗中不常见的毒性。
