Trastuzumab - A review of its use in the treatment of metastatic breast cancer overexpressing HER2
Trastuzumab - A review of its use in the treatment of metastatic breast cancer overexpressing HER2
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DOI：
10.2165/00003495-200262010-00008
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发表时间：
2002-01-01
期刊：
影响因子：
11.5
通讯作者：
Perry, CM
中科院分区：
文献类型：
--
作者：
McKeage, K;Perry, CM
曲妥珠单抗是一种人源化单克隆抗体，开发用于靶向HER 2受体，该受体被一些癌细胞过度表达，包括25%至30%的乳腺癌。曲妥珠单抗与HER 2的胞外结构域高亲和力结合，抑制过表达HER 2的肿瘤细胞的增殖。一项大型welt设计的多中心研究发现，将曲妥珠单抗添加到蒽环类药物加环磷酰胺或紫杉醇中，作为过表达HER 2受体的转移性乳腺癌的一线治疗，显著增加了疾病进展的滴度、客观缓解率，与单独化疗相比，曲妥珠单抗单药治疗与15%的广泛预治疗的过度表达HER 2的转移性乳腺癌患者和2670名先前未治疗的患者的客观反应相关，使用免疫组织化学（IHC）检测HER 2过表达水平为3+的患者检测或使用荧光原位杂交（FISH）的阳性HER 2结果，从曲妥珠单抗治疗中获益大于肿瘤过表达水平为2+的患者曲妥珠单抗已经在临床前证明了与几种化疗剂的协同作用，但临床上的最佳组合尚未确定。大多数患者通常耐受良好：最显著的不良反应是急性发热和/或寒战，并可能导致心功能障碍。严重不良事件，包括过敏反应和死亡，发生在0.25%的患者。症状性或无症状性心功能不全发生在27%的患者接受蒽环类药物和环磷酰胺联合曲妥珠单抗。因此，不推荐与蒽环类药物联合治疗。有症状或无症状的心功能不全发生在13%的患者接受曲妥珠单抗加紫杉醇和4.7%的患者接受曲妥珠单抗单独Conclusion：静脉曲妥珠单抗是有效的作为一个单一的代理，并与化疗相结合，它显着提高了中位疾病进展时间和生存时间的转移性乳腺癌患者过度表达HER 2受体相比，单独化疗。药物毒性是治疗的主要问题;特别是在既存心功能不全的患者、老年患者以及与蒽环类药物联合或在蒽环类药物治疗后。曲妥珠单抗适用于与紫杉醇联合作为一线治疗，或作为二线或三线治疗方案中的单药用于过度表达HER 2的转移性乳腺癌患者。正在进行研究，以确定含曲妥珠单抗和抗抑郁药的最佳联合方案。此外，目前的研究集中在最佳时机，测序和治疗持续时间，以及在新辅助和辅助设置管理。
Trastuzumab is a humanised monoclonal antibody developed to target the HER2 receptor which is overexpressed by some cancer cells, including 25 to 30% of breast cancers. Binding with high affinity to the extracellular domain of HER2, trastuzumab inhibits the proliferation of tumour cells that overexpress HER2.A large welt designed multicentre study found that the addition of trastuzumab to either an anthracycline plus cyclophosphamide or to paclitaxel, as first-line therapy for metastatic breast cancer overexpressing the HER2 receptor, significantly increased titre to disease progression, rate of objective response, duration of response and survival compared with chemotherapy alone.Single-agent trastuzumab was associated with an objective response in 15% of extensively pretreated patients with metastatic breast cancer overexpressing HER2, and 2670 of previously untreated patients, Patients with a HER2 overexpression level of 3+ using immunohistochemical (IHC) assay or a positive HER2 result using fluorescence in situ hybridisation (FISH), benefit more from trastuzumab therapy than those with tumours overexpressing at a level of 2+.Trastuzumab has demonstrated synergistic action with several chemotherapy agents preclinically but the optimal combination clinically is yet to be determined.Trastuzumab is generally well tolerated by most patients: the most significant adverse effects being acute fever and/or chills and the potential to cause cardiac dysfunction. Serious adverse events, including anaphylaxis and death, have occurred in 0.25% of patients.Symptomatic or asymptomatic cardiac dysfunction occurred in 27% of patients receiving an anthracycline and cyclophosphamide combined with trastuzumab. Thus, combination therapy with anthracyclines is not recommended. Symptomatic or asymptomatic cardiac dysfunction occurred in 13% of patients receiving trastuzumab plus paclitaxel and in 4.7% of patients receiving trastuzumab alone.Conclusion: Intravenous trastuzumab is effective as a single-agent, and in combination with chemotherapy it significantly improves the median time to disease progression and survival time in patients with metastatic breast cancer overexpressing the HER2 receptor compared with chemotherapy alone. Cardiotoxicity is the main concern with therapy; particularly in patients with pre-existing cardiac dysfunction, the elderly and in combination with, or following, anthracyclines. Trastuzumab is indicated for use with paclitaxel as first-line therapy or as a single agent in second- or third-line treatment regimens for patients with metastatic breast cancer overexpressing HER2. Investigation is ongoing to ascertain the optimal combination regimen containing trastuzumab and antineoplastic agents. In addition, current research is focusing on the optimal timing, sequencing and duration of therapy as well as administration in the neoadjuvant and adjuvant setting.