Evaluation of monoclonal humanized anti-HER2 antibody, trastuzumab, in patients with recurrent or refractory ovarian or primary peritoneal carcinoma with overexpression of HER2: A phase II trial of the Gynecologic Oncology Group
Evaluation of monoclonal humanized anti-HER2 antibody, trastuzumab, in patients with recurrent or refractory ovarian or primary peritoneal carcinoma with overexpression of HER2: A phase II trial of the Gynecologic Oncology Group
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DOI：
10.1200/jco.2003.10.104
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发表时间：
2003-01-15
影响因子：
45.3
通讯作者：
Horowitz, IR
中科院分区：
文献类型：
--
作者：
Bookman, MA;Darcy, KM;Horowitz, IR
目的：评估靶向人类表皮生长因子受体2（HER2）/NEU受体的单位单克隆抗体治疗的可行性，毒性和功效具有2+或3+ HER2的上皮卵巢或原发性腹膜癌免疫组织化学记录的过表达。静脉注射曲妥珠单抗最初以4 mg/kg的剂量给药，然后每周以2 mg/kg为单位。没有进行性疾病或过度毒性的患者可以无限期地继续治疗。在进展时，以较高的每周剂量（4 mg/kg）提供了在8周时稳定或反应疾病的人。分析了患者血清的HER2可溶性细胞外结构域，针对曲妥珠单抗的宿主抗体和曲妥珠单抗药代动力学的抗体：总共筛选了837个肿瘤样品以进行HER2表达，并表现出95例（11.4％）（11.4％）（11.4％）（11.4％） /3+表达水平。四十五名患者，所有患者接受了事先化疗，41例被认为符合条件和可评估。只有轻度的预期毒性，没有与治疗有关的死亡。尽管在24名患者中有8名检测到HER2的可溶细胞外域的升高水平，但血清HER2与临床结局无关。没有证据表明宿主抗抗蛋白酶形成抗体形成。曲妥珠单抗的血清浓度随着持续治疗而逐渐增加。总回应率为7.3％，其中包括一个完整和两个部分响应。中位治疗持续时间为8周（范围为2至104周），无进展间隔为2.0个月。结论：复发性卵巢癌中单药曲妥珠单抗的临床值受HER2过表达的低频和低频的限制。 HER2过表达患者的客观反应率。 （c）2003年美国临床肿瘤学会。
Purpose: To evaluate the feasibility, toxicity, and efficacy of single-agent monoclonal antibody therapy targeting the human epidermal growth factor receptor 2 (HER2)/neu receptor in ovarian and primary peritoneal carcinoma.Patients and Methods: Eligible patients had measurable persistent or recurrent epithelial ovarian or primary peritoneal carcinoma with 2+ or 3+ HER2 overexpression documented by immunohistochemistry. Intravenous trastuzumab was administered initially at a dose of 4 mg/kg, then weekly at 2 mg/kg. Patients without progressive disease or excessive toxicity could continue treatment indefinitely. Those with stable or responding disease at 8 weeks were offered treatment at a higher weekly dose (4 mg/kg) at time of progression. Patient sera were analyzed for the presence of the soluble extracellular domain of HER2, host antibodies against trastuzumab, and trastuzumab pharmacokinetics.Results: A total of 837 tumor samples were screened for HER2 expression, and 95 patients (11.4%) exhibited the requisite 2+/3+ expression level. Forty-five patients, all of whom received prior chemotherapy, were entered, and 41 were deemed eligible and assessable. There were only mild expected toxicities and no treatment-related deaths. Although an elevated level of the soluble extracellular domain of HER2 was detected in eight of 24 patients, serum HER2 was not associated with clinical outcome. There was no evidence of host antitrostuzumab antibody formation. Serum concentrations of trastuzumab gradually increased with continued therapy. An overall response rate of 7.3% included one complete and two partial responses. Median treatment duration was 8 weeks (range, 2 to 104 weeks), and median progression-free interval was 2.0 months.Conclusion: The clinical value of single-agent trastuzumab in recurrent ovarian cancer is limited by the low frequency of HER2 overexpression and low rate of objective response among patients with HER2 overexpression. (C) 2003 by American Society of Clinical Oncology.