Humanized monoclonal antibodies Herceptin

An interaction of doxorubicin with the anti-HER2 receptor humanized monoclonal antibody, trastuzumab (Herceptin), has been reported. Most patients who received trastuzumab in early trials had been pretreated with anthracyclines. Despite this, preliminary information suggested that reduced systolic cardiac function was an adverse effect of trastuzumab (119). More recently, this problem has been further highlighted in a study of women with metastatic breast cancer (120). Patients who had not received prior anthracycline-containing adjuvant chemotherapy were at greater risk of cardiotoxicity when they received trastuzumab in combination with doxorubicin or cyclophosphamide (27 and 75% respectively), compared with only 11% of patients who received trastuzumab in combination with pachtaxel (120,121). The risk of cardiac events in patients treated with doxorubicin, cyclophosphamide, and trastuzumab increased markedly after a cumulative doxorubicin dose of 360 mg/m. This suggests synergistic cardiotoxicity with trastuzumab and doxorubicin. Trastuzumab is therefore currently licensed only for use in conjunction with pacli-taxel or docetaxel and not with conventional doxorubicin. 

Trastuzumab (Herceptin) is a humanized monoclonal antibody against the HER2/neu (ErbB-2) member of the epidermal growth factor family of cellular receptors. The internal domain of the HER2/neu glycoprotein encodes a tyrosine kinase that activates downstream signals and enhances metastatic potential and inhibits apoptosis. HER2/neu is overexpressed in up to 30% of breast cancers and is associated with clinical resistance to cytotoxic and hormone therapy. A number of mechanisms of action have... 

In precfinical studies, the combination of Bevacizumab with chemotherapy led to synergistic activity. In xenotransplants, the combination of Bevacizumab with capecitabine inhibited tumor growth more effectively and longer than any other tested substance (Sachsenmaier 2001). It also showed synergistic effects in combination with paclitaxel and Trastuzumab (Herceptin ), a humanized monoclonal antibody that acts on the HER2/neu (erbB2) receptor. In further in-vivo studies, the application of Bevacizumab to animals previously treated with capecitabine, topotecan, or cis-platin showed more successful tumor suppression. Also, repeated application of Bevacizumab proved to be safe and well tolerated. 

Trastuzumab (Herceptin) is a humanized monoclonal antibody against the extracellular domain of the human epidermal growth factor receptor 2 (HER2). Treatment of cancer patients with trastuzumab has been associated with an increased incidence of cardiac toxicity including left ventricular cardiac dysfunction, arrhythmias, hypertension, disabling cardiac failure, cardiomyopathy, and cardiac death. Trastuzumab can also cause asymptomatic decline in left ventricular ejection fraction (LVEF) (Herceptin PI 2010). 

Trastuzumab (Herceptin) -humanized mouse monoclonal antibody directed against HER-2/new receptor -fevers, chills, nausea, vomiting, headache during administration -cardiotoxicity (the FDA has not approved concurrent use with doxorubicin)... 

Antibodies and derivatives Trastuzumab, humanized monoclonal IgGl against HER2 Herceptin Lyophilized, sterile powder nominally containing 440 mg IV Depends on HER-2 concentration (-5.1)... 

First-line treatment of her metastatic breast cancer should therefore incorporate the monoclonal antibody trastuzumab (Herceptin). NICE (2002b) have issued a technology appraisal on the use of trastuzumab in metastatic breast cancer which states that trastuzumab be used in combination with paclitaxel for women with tumours with excessive human epidermal growth factor receptor 2 (HER2) at levels of 3+ who have not had chemotherapy for metastatic breast cancer and for whom anthracycline treatment is inappropriate. ... 

Molina, M. A., Codony-Servat, J., Albanell, J., Rojo, F., Arribas, J., and Baselga, J. (2001). Trastuzumab (herceptin), a humanized anti-Her2 receptor monoclonal antibody, inhibits basal and activated Her2 ectodomain cleavage in breast cancer cells. Cancer Res. 61, 4744-4749. 

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