Department of Breast Medical Oncology, Division of Pharmacy, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Pharmacotherapy. 2009 Dec;29(12):1482-90. doi: 10.1592/phco.29.12.1482.
Metastatic breast cancer is considered incurable. Despite effective response rates achieved with anthracycline or taxane anticancer drugs, cancers in approximately one third of patients fail to respond to first-line treatment with these agents. Patients who do respond show disease progression after a median of approximately 7-8 months. As a consequence, the development of new salvage treatments and strategies for metastatic breast cancer continues to be a high priority. However, few randomized controlled trials have been conducted in patients in whom previous treatment with anthracyclines and taxanes fails. Among those trials that have, few demonstrated an improvement in overall survival. Overall survival is considered the gold standard for evaluating the benefits of experimental cancer therapies. In addition, many investigators use progression-free survival or time to progression. Survival outcomes from large trials of newer combinations, such as ixabepilone plus capecitabine and gemcitabine plus vinorelbine, are encouraging. They have shown significant benefits in terms of progression-free survival, and they have revealed demonstrable benefits for several hard-to-treat subgroups of patients with metastatic breast cancer. Addition of the targeted agents trastuzumab, bevacizumab, and lapatinib to chemotherapy has produced significant benefits in time to progression and progression-free survival. Ongoing research should help in determining which patients are likely to benefit from such agents when first- or second-line therapy fails and in ascertaining whether this therapy can be optimized to maximize therapeutic potential and minimize unnecessary toxicity.
转移性乳腺癌被认为是无法治愈的。尽管使用蒽环类或紫杉烷类抗癌药物可以有效缓解病情，但仍有约三分之一的患者对这些药物的一线治疗没有反应。对这些药物有反应的患者在大约 7-8 个月的中位时间后会出现疾病进展。因此，开发新的挽救性治疗方法和转移性乳腺癌的策略仍然是当务之急。然而，在先前接受蒽环类和紫杉烷类药物治疗失败的患者中，很少进行随机对照试验。在进行了这些试验的患者中，很少有患者的总生存期得到改善。总生存期被认为是评估实验性癌症治疗益处的金标准。此外，许多研究人员使用无进展生存期或进展时间。对于新型联合治疗（如伊沙匹隆加卡培他滨和吉西他滨加长春瑞滨）的大型试验的生存结果令人鼓舞。它们在无进展生存期方面显示出显著的益处，并且对转移性乳腺癌的几个难以治疗的亚组患者也显示出明显的益处。将靶向药物曲妥珠单抗、贝伐珠单抗和拉帕替尼加入化疗中，可以显著提高进展时间和无进展生存期。正在进行的研究应有助于确定哪些患者在一线或二线治疗失败时可能从这些药物中获益，并确定是否可以优化这种治疗以最大限度地发挥治疗潜力并最小化不必要的毒性。
