• J Baselga.
• Medical Oncology Service, Hospital Universitari Vall d'Hebron, and the Universidad Autonoma de Barcelona, Spain.
• Semin. Oncol. 2000 Oct 1; 27 (5 Suppl 9): 27-32.

AbstractTrastuzumab (Herceptin; Genentech, Inc, So. San Francisco, CA) is a high-affinity, humanized anti-HER2 antibody that has shown benefit in the therapy of patients with metastatic HER2-overexpressing breast cancer. Results from initial clinical trials of trastuzumab as a single agent or in combination with chemotherapy established important guidelines for the therapy of HER2-positive tumors, but represent an early phase of clinical development. Preclinical studies have shown additive and synergistic effects of trastuzumab when given in combination with several chemotherapeutic agents, and a series of clinical trials exploring these new combinations is under way or will be started shortly. Substantial effort will be directed toward promising schedules and combinations, such as weekly paclitaxel with trastuzumab or combinations of platinum, taxanes, and trastuzumab. Due to the unexpected cardiac toxicity observed with the combination of doxorubicin plus trastuzumab, new studies will be designed to prospectively assess cardiac function and will incorporate anthracyclines with less cardiotoxicity, such as liposomal doxorubicin. Combination studies are not limited to cytotoxic agents, as laboratory and clinical data have demonstrated that HER2 overexpression results in resistance to hormonal therapy. Therefore, a series of studies combining hormonal treatments with trastuzumab is being considered. Finally, the integration of trastuzumab into the adjuvant and neoadjuvant settings will be studied by United States and European cooperative groups.

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