Efficacy and safety of trastuzumab as a single agent in heavily pretreated patients with HER-2/NEU-overexpressing metastatic breast cancer
Efficacy and safety of trastuzumab as a single agent in heavily pretreated patients with HER-2/NEU-overexpressing metastatic breast cancer
复制标题
DOI：
10.1177/030089160409000110
复制
发表时间：
2004-01-01
期刊：
影响因子：
1.9
通讯作者：
Hatake, K
中科院分区：
文献类型：
--
作者：
Sawaki, M;Ito, Y;Hatake, K
目的和背景：人表皮生长因子受体2 （HER2）蛋白是针对过表达HER-2/neu基因的乳腺癌的抗体治疗的一个独特而有用的靶点。重组人源化抗her2单克隆抗体曲妥珠单抗于1998年在美国被批准用于临床。它于2001年6月在日本上市。本研究的重点是曲妥珠单抗作为单药治疗HER2/ new过表达转移性乳腺癌的二线和三线治疗的有效性和安全性。研究设计：在2001年6月至2002年5月期间，我们用曲妥珠单抗治疗62例患者，作为单药或联合化疗，用于her2过表达转移性乳腺癌的二三线治疗。62例患者中有27例接受单药曲妥珠单抗治疗。我们回顾性地回顾了单药给药的有效性和安全性。免疫组化染色检测HER2的表达。所有患者接受标准负荷剂量4mg /kg，随后每周2mg /kg。结果：患者平均每周输注16.7次（范围1-66次）。曲妥珠单抗治疗通常耐受性良好。临床严重不良事件（3级或4级）包括低血压（7.4%）和缺氧（3.7%）。1 ~ 2级毒性包括发热（11.1%）和腹泻（3.7%）。输液相关反应很少，严重的血液学并发症也很少。该研究未发生心脏毒性。3例完全缓解，3例部分缓解，3例无变化，17例病情进展，1例未进行评估。有资料的26例患者的总有效率为23.1%（95%可信区间为5.7-40.4）。中位缓解持续时间为6.4个月（范围2.5-14.0）。中位进展时间为3.1个月（范围0.2-16.7）。不同转移部位的反应率差异如下：肺0%(0/12)，骨10.0%(1/10)，肝0%(0/8)，皮肤50.0%(4/8)，淋巴结42.9%(3/7)，脑0%（0/2）。结论：分子靶向治疗曲妥珠单抗似乎是安全的，并且通常耐受性良好。对于转移性乳腺癌的治疗，单药治疗在一些患者中产生持久的反应，但缺乏足够的疗效。单药使用曲妥珠单抗是治疗无内脏转移的非危及生命疾病的可行选择。
Aims and background: The human epidermal growth factor receptor 2 (HER2) protein is a unique and useful target for antibody therapy against breast cancers that overexpress the HER-2/neu gene. The recombinant humanized anti-HER2 monoclonal antibody, trastuzumab, was approved for clinical use in the United States in 1998. It became available in Japan in June 2001. This study focuses on the efficacy and safety of trastuzumab as a single agent in second-third line treatment of HER2/neu-overexpressing metastatic breast cancer. Study design: Between June 2001 and May 2002, we treated 62 patients with trastuzumab, as a single agent or in combination chemotherapy, for second-third line treatment of HER2-over-expressing metastatic breast cancer. Twenty-seven of 62 patients were treated with trastuzumab as a single agent. We reviewed retrospectively the efficacy and safety of the drug given as a single agent. The expression of HER2 was determined by immunohistochemical staining. All patients received a standard loading dose of 4 mg/kg followed by 2 mg/kg weekly.Results: Patients received a median of 16.7 weekly infusions (range, 1-66 infusions). Trastuzumab therapy was generally well tolerated. Clinically severe adverse events (grade 3 or 4) included hypotension (7.4%), and hypoxia (3.7%). Grade 1 to 2 toxicity included fever (11.1%) and diarrhea (3.7%). Infusion-related reactions were infrequent, as were serious hematologic complications. Cardiotoxicity did not occur in the study. Three patients had a complete and 3 a partial response, 3 had no change, 17 had progressive disease, and one was not evaluated. The overall response rate in the 26 patients with available data was 23.1% (95% confidence interval, 5.7-40.4). The median duration of response was 6.4 months (range, 2.5-14.0). The median time to progression was 3.1 months (range, 0.2-16.7). Response rates differed by metastatic site as follows: lung 0% (0/12), bone 10.0% (1/10), liver 0% (0/8), skin 50.0% (4/8), lymph nodes 42.9% (3/7), brain 0% (0/2).Conclusions: Molecular target therapy with trastuzumab appears safe and is generally well tolerated. For treatment of metastatic breast cancer, single agent therapy produces a durable response in some patients but lacks sufficient efficacy. Single agent use of trastuzumab is a viable option for treatment in cases with non-life-threatening disease without visceral metastasis.