Phase II study of weekly intravenous recombinant humanized Anti-p185(HER2) monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast
Phase II study of weekly intravenous recombinant humanized Anti-p185(HER2) monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast
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DOI：
10.1200/jco.1996.14.3.737
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发表时间：
1996-03-01
影响因子：
45.3
通讯作者：
Norton, L
中科院分区：
文献类型：
--
作者：
Baselga, J;Tripathy, D;Norton, L
目的：乳腺癌经常过度表达原癌基因HER2的产物，它是一种185kd的生长因子受体(P185(HER2))。重组人源化单抗(RhuMAb)HER2与p185(HER2)具有高亲和力，并抑制过表达HER2的乳腺癌细胞的生长。我们评价了每周静脉注射rhuMAb HER2治疗HER2高表达的转移性乳腺癌患者的疗效和毒性。患者接受250 mg静脉注射大黄单抗HER2的负荷量，然后每周10次，每次100 mg。在这个治疗周期结束时没有疾病进展的患者被提供100 mg/wk的维持期。结果：研究患者有广泛的转移性疾病，并且大多数都接受过广泛的先前的抗癌治疗。90%的患者获得了合适的rhuMAb HER2药代动力学水平。毒性很小，所有患者都没有检测到rhuMAb HER2抗体，在43例可评估的患者中，有5例出现客观反应，包括1例完全缓解和4例部分缓解(总有效率为11.6%，95%可信区间为4.36~25.9)。在肝脏、纵隔、淋巴结和胸壁病变中观察到有反应。两名患者出现轻微反应，14名患者出现稳定疾病，中位持续时间为5.1个月。结论：rhuMAb HER2在接受过广泛治疗的HER2高表达转移性乳腺癌患者中耐受性和临床活性良好。这是靶向生长因子受体可以导致人类癌症消退的证据，并证明了对该药物的进一步评估。(C)1996年，由美国临床肿瘤学会主办。
Purpose: Breast cancer frequently overexpresses the product of the HER2 proto-oncogene, a 185-kd growth factor receptor (p185(HER2)). The recombinant humanized monoclonal antibody (rhuMAb) HER2 has high affinity for p185(HER2) and inhibits the growth of breast cancer cells that overexpress HER2. We evaluated the efficacy and toxicity of weekly intravenous administration of rhuMAb HER2 in patients with HER2-overexpressing metastatic breast cancer.Patients and Methods: We treated 46 patients with metastatic breast carcinomas that overexpressed HER2. Patients received a loading dose of 250 mg of intravenous rhuMAb HER2, then 10 weekly doses of 100 mg each. Patients with no disease progression at the completion of this treatment period were offered a maintenance phase of 100 mg/wk.Results: Study patients had extensive metastatic disease, and most had received extensive prior anticancer therapy. Adequate pharmacokinetic levels of rhuMAb HER2 were obtained in 90% of the patients. Toxicity was minimal and no antibodies against rhuMAb HER2 were detected in any patients, Objective responses were seen in five of 43 assessable patients, and included one complete remission and four partial remissions (overall response rate, 11.6%; 95% confidence interval, 4.36 to 25.9). Responses were observed in liver, mediastinum, lymph nodes, and chest wall lesions. Minor responses, seen in two patients, and stable disease, which occurred in 14 patients, lasted for a median of 5.1 months.Conclusion: rhuMAb HER2 is well tolerated and clinically active in patients with HER2-overexpressing metastatic breast cancers that had received extensive prior therapy. This is evidence that targeting growth factor receptors can cause regression of human cancer and justifies further evaluation of this agent. (C) 1996 by American Society of Clinical Oncology.