Pegram M D, Lipton A, Hayes D F, Weber B L, Baselga J M, Tripathy D, Baly D, Baughman S A, Twaddell T, Glaspy J A, Slamon D J
Department of Medical Oncology, The University of California at Los Angeles, USA.
J Clin Oncol. 1998 Aug;16(8):2659-71. doi: 10.1200/JCO.1998.16.8.2659.
To determine the toxicity, pharmacokinetics, response rate, and response duration of intravenous (i.v.) administration of recombinant, humanized anti-p185HER2 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.
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 i.v.) on day 0, followed by weekly doses of 100 mg i.v. for 9 weeks. Patients received CDDP (75 mg/m2) on days 1, 29, and 57.
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.
The use of rhuMAb HER2 in combination with CDDP in patients with HER2/neu-overexpressing metastatic breast cancer results in objective clinical response rates 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 HER2 was unaffected by coadministration with CDDP.
在一项针对HER2/neu过表达转移性乳腺癌患者的II期、开放标签、多中心临床试验中，确定静脉注射重组人源化抗p185HER2单克隆抗体（rhuMAb HER2）联合顺铂（CDDP）的毒性、药代动力学、缓解率及缓解持续时间。
研究人群包括在标准化疗期间接受过广泛预处理、HER2/neu过表达且疾病进展的晚期乳腺癌患者。患者在第0天接受rhuMAb HER2负荷剂量（静脉注射250 mg），随后每周静脉注射100 mg，共9周。患者在第1、29和57天接受CDDP（75 mg/m²）。
在37例可评估缓解情况的患者中，9例（24.3%）达到部分缓解（PR），9例（24.3%）有轻微缓解或疾病稳定，19例（51.3%）疾病进展。中位缓解持续时间为5.3个月（范围1.6 - 18个月）。39例患者中有22例（56%）观察到III级或IV级毒性。毒性特征反映了单独使用CDDP时预期的情况，最常见的毒性为血细胞减少（n = 10）、恶心/呕吐（n = 9）和乏力（n = 5）。CDDP的联合使用未改变rhuMAb HER2的平均药代动力学参数。
HER2/neu过表达转移性乳腺癌患者使用rhuMAb HER2联合CDDP可使客观临床缓解率高于既往单独报道的CDDP或rhuMAb HER2的缓解率。此外，联合使用并未导致毒性明显增加。最后，rhuMAb HER2的药理学不受与CDDP联合使用的影响。
