Phase II study of receptor-enhanced chemosensitivity using recombinant humanized anti-p185HER2/neu monoclonal antibody plus cisplatin in patients with HER2/neu-overexpressing metastatic breast cancer refractory to chemotherapy treatment
Phase II study of receptor-enhanced chemosensitivity using recombinant humanized anti-p185HER2/neu monoclonal antibody plus cisplatin in patients with HER2/neu-overexpressing metastatic breast cancer refractory to chemotherapy treatment
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DOI：
10.1200/jco.1998.16.8.2659
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发表时间：
1998-08-01
影响因子：
45.3
通讯作者：
Slamon, DJ
中科院分区：
文献类型：
--
作者：
Pegram, MD;Lipton, A;Slamon, DJ
目的：在一项针对 HER2/neu 过度表达的转移性乳腺癌患者的 II 期、开放标签、多中心临床试验中，确定静脉 (IV) 注射重组人源化抗 p185(HER2) 单克隆抗体 (rhuMAb HER2) 加顺铂 (CDDP) 的毒性、药代动力学、反应 Kite 和反应持续时间。 患者和方法：研究人群包括接受过广泛预处理的晚期乳腺癌患者标准化疗期间 HER2/neu 过度表达和疾病进展。患者在第 0 天接受负荷剂量的 rhuMAb HER2（250 mg IV），随后每周接受 100 mg IV 剂量，持续 9 周。患者在第 1、29 和 57 天接受 CDDP (75 mg/m(2))。 结果：在 37 名可评估缓解的患者中，9 名 (24.3%) 达到 PR，9 名 (24.3%) 出现轻微缓解或疾病稳定，19 名 (51.3%) 发生疾病进展。中位缓解持续时间为 5.3 个月（范围：1.6-18）。 39 名患者中有 22 名 (56%) 观察到 III 级或 IV 级毒性。毒性特征反映了单独使用 CDDP 的预期，最常见的毒性是血细胞减少 (n = 10)、恶心/呕吐 (n = 9) 和乏力 (n = 5)。 rhuMAb HER2 的平均药代动力学参数未因 CDDP 的共同给药而改变。 结论：在 HER2/neu 过表达的转移性乳腺癌患者中联合使用 rhuMAb HER2 与 CDDP 所产生的客观临床反应 Kites 高于先前报道的单独使用 CDDP 或单独使用 rhuMAb HER2 的结果。此外，该组合不会导致毒性明显增加。最后，rhuMAb HEW 的药理学不受与 CDDP 共同给药的影响。 J 临床肿瘤学杂志 16：2659-2671。 (C) 1998 年美国临床肿瘤学会。
Purpose: To determine the toxicity, pharmacokinetics, response Kite, and response duration of intravenous (IV) administration of recombinant, humanized anti-p185(HER2) monoclonal antibody (rhuMAb HER2) plus cisplatin (CDDP) in a phase II, open-label, multicenter clinical trial for patients with HER2/neu-overexpressing metastatic breast cancer.Patients and Methods: The study population consisted of extensively pretreated advanced breast cancer patients with HER2/neu overexpression and disease progression during standard chemotherapy. Patients received a loading dose of rhuMAb HER2 (250 mg IV) on day 0, followed by weekly doses of 100 mg IV for 9 weeks. Patients received CDDP (75 mg/m(2)) on days 1, 29, and 57.Results: Of 37 patients assessable for response, nine (24.3%) achieved a PR, nine (24.3%) had a minor response or stable disease, and disease progression occurred in 19 (51.3%). The median response duration was 5.3 months (range, 1.6-18). Grade III or IV toxicity was observed in 22 of 39 patients (56%). The toxicity profile reflected that expected from CDDP alone with the most common toxicities being cytopenias (n = 10), nausea/vomiting (n = 9), and asthenia (n = 5). Mean pharmacokinetic parameters of rhuMAb HER2 were unaltered by coadministration of CDDP.Conclusion: The use of rhuMAb HER2 in combination with CDDP in patients with HER2/neu-overexpressing metastatic breast cancer results in objective clinical response Kites higher than those reported previously for CDDP alone, or rhuMAb HER2, alone. In addition, the combination results in no apparent increase in toxicity. Finally, the pharmacology of rhuMAb HEW was unaffected by coadministration with CDDP. J Clin Oncol 16: 2659-2671. (C) 1998 by American Society of Clinical Oncology.