Antibodies as molecular target-based therapy: trastuzumab.
The HER2 gene is overexpressed or amplified in approximately 30% of breast cancers. Breast cancer patients with HER2 overexpression or amplification have shortened disease-free and overall survivals. The HER2 protein is thought to be a unique and useful target for antibody therapy of cancers overexpressing the HER2 gene. The recombinant humanized anti-HER2 monoclonal antibody, trastuzumab (Herceptin) is now available for clinical use. In a large phase II trial, trastuzumab produced a favorable response rate as a single agent in patients with metastatic breast cancer who had received one or two prior chemotherapies. Furthermore, a large phase III trial showed that trastuzumab plus chemotherapy as a first-line treatment for metastatic breast cancer significantly improved response rate, time to disease progression, and overall survival compared with chemotherapy alone. As a single agent and in combination with chemotherapy, trastuzumab was generally well tolerated. Thus, trastuzumab plays an important role in the treatment strategy of metastatic breast cancer overexpressing HER2 protein. In this article, details of this novel biologic agent are reviewed, in conjunction with an overview of clinical studies performed in Japan.
Tokuda
Yutaka
Y
Department of Surgery, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa 259-1193, Japan. tokuda@is.icc.u-tokai.ac.jp
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D001943:Breast Neoplasms / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D015195:Drug Design; D005260:Female; D006801:Humans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D000068878:Trastuzumab; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab