Baselga J, Tripathy D, Mendelsohn J, Baughman S, Benz C C, Dantis L, Sklarin N T, Seidman A D, Hudis C A, Moore J, Rosen P P, Twaddell T, Henderson I C, Norton L
Department of Medicine, Services of Breast and Gynecological Cancer Medicine and Clinical Immunology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Semin Oncol. 1999 Aug;26(4 Suppl 12):78-83.
The HER2/neu proto-oncogene is overexpressed in 25% to 30% of patients with breast cancer. Trastuzumab (Herceptin; Genentech, San Francisco, CA), a recombinant humanized monoclonal antibody with high affinity for the HER2 protein, inhibits the growth of breast cancer cells overexpressing HER2. In this phase II study the efficacy and toxicity of weekly administration of trastuzumab was evaluated in 46 patients with metastatic breast cancer whose tumors overexpressed HER2. A loading dose of 250 mg trastuzumab was administered intravenously, which was followed by 10 weekly doses of 100 mg each. Upon completion of this treatment period, patients with no disease progression could receive a weekly maintenance dose of 100 mg. Patients in this trial had extensive metastatic disease, and most had received prior anticancer therapy. Ninety percent of patients achieved adequate serum levels of trastuzumab. Toxicity was minimal, and no antibodies against trastuzumab could be detected. Objective responses were observed in 5 of the 43 evaluable patients, which included 1 complete remission and 4 partial remissions, for an overall response rate of 11.6%. Responses were seen in mediastinum, lymph nodes, liver, and chest wall lesions. Minor responses (seen in 2 patients) and stable disease (14 patients) lasted for a median of 5.1 months. These results demonstrate that trastuzumab is well tolerated and clinically active in patients with HER2-overexpressing metastatic breast cancers who have received extensive prior therapy. The regression of human cancer through the targeting of putative growth factor receptors such as HER2 warrants further evaluation of trastuzumab in the treatment of breast cancer.
HER2/neu原癌基因在25%至30%的乳腺癌患者中过度表达。曲妥珠单抗（赫赛汀；基因泰克公司，加利福尼亚州旧金山）是一种对HER2蛋白具有高亲和力的重组人源化单克隆抗体，可抑制过度表达HER2的乳腺癌细胞生长。在这项II期研究中，对46例肿瘤过度表达HER2的转移性乳腺癌患者评估了每周使用曲妥珠单抗的疗效和毒性。静脉注射250mg曲妥珠单抗的负荷剂量，随后每周注射10剂，每剂100mg。在这个治疗期结束后，没有疾病进展的患者可以接受每周100mg的维持剂量。该试验中的患者有广泛的转移性疾病，大多数患者之前接受过抗癌治疗。90%的患者达到了曲妥珠单抗的足够血清水平。毒性极小，未检测到抗曲妥珠单抗的抗体。在43例可评估患者中的5例观察到客观反应，包括1例完全缓解和4例部分缓解，总缓解率为11.6%。在纵隔、淋巴结、肝脏和胸壁病变中观察到反应。轻微反应（2例患者）和疾病稳定（14例患者）持续的中位时间为5.1个月。这些结果表明，曲妥珠单抗在接受过广泛前期治疗的HER2过度表达转移性乳腺癌患者中耐受性良好且具有临床活性。通过靶向HER2等假定的生长因子受体使人类癌症消退，值得进一步评估曲妥珠单抗在乳腺癌治疗中的作用。
