Moreno-Aspitia Alvaro, Perez Edith A
College of Medicine, Division of Hematology and Oncology, Mayo Clinic, Jacksonville, Florida 32224, USA.
Clin Ther. 2009 Aug;31(8):1619-40. doi: 10.1016/j.clinthera.2009.08.005.
As many as 30% of women diagnosed with early breast cancer (BC) will eventually progress to or relapse with locally advanced or meta-static BC. Resistance to the commonly used chemotherapies anthracyclines and taxanes, as well as the approval of new pharmacologic options for treating BC, present important clinical, cost-effectiveness, and societal challenges.
The aims of this work were as follows: (1) to review published evidence for potential management strategies, particularly with new therapies, for women with resistant, recurrent, or metastatic BC who have been previously treated with anthracyclines and/or taxanes; and (2) to discuss the wider burden of disease on the patient and society, and potential implications for payers and health care decision makers.
The PubMed database and relevant congress abstract databases were searched to identify clinical data with relevance to the treatment of recurrent or metastatic BC resistant to anthracyclines and/or taxanes. No date limits were applied, and the search was current as of April 17, 2009. No specific inclusion or exclusion criteria were applied; preference was given to Phase II or III clinical trials published within the past 10 years, although older studies were included if they contained data that guides current clinical practice.
Sixteen of the most relevant Phase II or III studies were identified for the 4 agents currently approved for use in this setting, including capecitabine alone (2 studies), capecitabine plus docetaxel (2 studies), ixabepilone alone (5 studies), ixabepilone plus capecitabine (3 studies), gemcitabine plus paclitaxel (1 study), and nanoparticle albumin-bound paclitaxel (3 studies), with overall response rates (complete plus partial responses) ranging from 11.5% to 57%. Other relevant studies are discussed for liposomal doxorubicin, docetaxel, paclitaxel, larotaxel, and vinorelbine, as well as for the addition of biologic agents such as trastuzumab, lapatinib, and bevacizumab to ongoing chemotherapeutic regimens in resistant or metastatic BC. However, only 4 studies discussed the cost of care and cost-effectiveness of current treatment options.
Previous research has reported the efficacy of capecitabine, gemcitabine, nanoparticle albumin-bound paclitaxel, and ixabepilone in the treatment of metastatic BC in patients who have already been treated with anthracyclines and/or taxanes. Such patients previously had few treatment options. Ongoing investigations into novel combination regimens with these agents, including combinations with targeted agents, may further build on this progress. Further research is needed to understand the economic implications of these regimens, including the broader societal effects and the value to patients.
多达30%被诊断为早期乳腺癌（BC）的女性最终会进展为局部晚期或转移性BC或出现复发。对常用化疗药物蒽环类和紫杉烷类产生耐药性，以及新的BC治疗药物选项获批，带来了重要的临床、成本效益和社会挑战。
本研究的目的如下：（1）回顾已发表的关于潜在管理策略的证据，尤其是针对先前接受过蒽环类和/或紫杉烷类治疗的耐药、复发或转移性BC女性的新疗法；（2）讨论疾病给患者和社会带来的更广泛负担，以及对支付方和医疗保健决策者的潜在影响。
检索PubMed数据库和相关会议摘要数据库，以识别与蒽环类和/或紫杉烷类耐药的复发或转移性BC治疗相关的临床数据。未设置日期限制，检索截至2009年4月17日。未应用特定的纳入或排除标准；优先选择过去10年内发表的II期或III期临床试验，不过如果较旧的研究包含指导当前临床实践的数据也会纳入。
针对目前批准用于该情况的4种药物，确定了16项最相关的II期或III期研究，包括单药卡培他滨（2项研究）、卡培他滨加多西他赛（2项研究）、单药伊沙匹隆（5项研究）、伊沙匹隆加卡培他滨（3项研究）、吉西他滨加紫杉醇（1项研究）和纳米白蛋白结合型紫杉醇（3项研究），总体缓解率（完全缓解加部分缓解）为11.5%至57%。还讨论了其他相关研究，涉及脂质体阿霉素、多西他赛、紫杉醇、拉罗他赛和长春瑞滨，以及在耐药或转移性BC的现行化疗方案中添加生物制剂如曲妥珠单抗、拉帕替尼和贝伐单抗。然而，只有4项研究讨论了当前治疗方案的护理成本和成本效益。
先前的研究报告了卡培他滨、吉西他滨、纳米白蛋白结合型紫杉醇和伊沙匹隆在治疗已接受蒽环类和/或紫杉烷类治疗的转移性BC患者中的疗效。这类患者以前几乎没有治疗选择。对这些药物的新型联合方案，包括与靶向药物的联合方案的持续研究，可能会在此基础上进一步取得进展。需要进一步研究以了解这些方案的经济影响，包括更广泛的社会影响和对患者的价值。
