Breast cancer, treatment trastuzumab

In addition to these breast cancer trials, trastuzumab is under evaluation for the treatment of other cancers in which HER2 overexpression can occur, including ovarian cancer, non-small cell lung cancer, colorectal cancer, and prostate cancer. 

Metastasized human epidermal growth factor receptor 2 (HER2)-expressing breast cancer treatment was the first indication for trastuzumab, a HER2-specific humanized monoclonal antibody. HER2 is a receptor tyrosine kinase of the EGER family that is overexpressed... 

Yeon CH, Pegram MD. Anti-erbB-2 antibody trastuzumab in the treatment of HER2-amplified breast cancer. Invest New Drugs 2005 23 391-409. 

Umemura, S., Sekido, Y., Itoh, H., and Osamura, RY. 2002. Pathological evaluation of HER2 overexpression for the treatment of metastatic breast cancers by humanized anti-HER2 monoclonal antibody (trastuzumab). Acta Histochemica et Cytochemica, Kyoto 35(2), 77-81. 

Goldenberg, M.M., "Trastuzumab, a Recombinant DNA Derived Monoclonal Antibody, a Novel Agent for the Treatment of Metastatic Breast Cancer," Clin. Ther., 21, 309-318 (1999). 

Trastuzumab is licensed for the treatment of early breast cancer that overexpresses human epidermal growth factor receptor-2 (HER2). It may be administered as monotherapy or in combination with, for example, paclitaxel, docetaxel (taxanes) or anastrozole (aromatase inhibitors). Since trastuzumab can cause cardiotoxicity, concomitant use with anthracyclines such as... 

Pegram MD, Konecny GE, O Callaghan C, Beryt M, Pietras R, Slamon DJ. Rational combinations of trastuzumab with chemotherapeutic drugs used in the treatment of breast cancer. J Natl Cancer Inst 2004 96 739-49. 

In Section 3.2.2 we presented data from a clinical trial comparing trastuzumab to observation only after adjuvant chemotherapy in HER2-positive breast cancer. The incidence rates in the test treatment and control groups were respectively 7.0 per cent and 4.7 per cent. 

Indications For treatment of patients with metastatic breast cancer whose tumors overexpress the HER2 protein and who have received one or more chemotherapy regimens for their metastatic disease. Trastuzumab in combination with pacli-taxel is also indicated for treatment of patients with metastatic breast cancer whose tumors overexpress HER2 protein and who have not received chemotherapy for their metastatic disease... 

Milano G, Lescaut W, Formento J et al. HER2 genetic polymorphism and pharmacodynamics of trastuzumab-based treatment in breast cancer patients. J Clin Oncol 2005 23 501. 

Trastuzumab is a recombinant DNA-derived, humanized monoclonal antibody that binds to the extracellular domain of the human epidermal growth factor receptor HER-2/ . This antibody blocks the natural ligand from binding and down-regulates the receptor. Trastuzumab is approved for the treatment of metastatic breast cancer in patients whose tumors overexpress HER-2/ . As a single agent it induces remission in about 15-20% of patients in combination with chemotherapy, it increases response rate and duration as well as 1-year survival. Trastuzumab is under investigation for other tumors that express HER-2... 

Trastuzumab is indicated as a single agent for the treatment of patients whose breast cancer has an overexpression of the HER-2 protein and has been previously treated by standard chemotherapeutic regimen. Trastuzumab is administered in combination with paclitaxel in patients who have not been previously treated with chemotherapy and their tumors overexpress HER-2. The initial dose for trastuzumab is 4 mg/kg given as a 90-min infusion, and the weekly maintenance dose is 2 mg/kg administered as a 30-min infusion. Its half-life is 1.7 and 12 days when a dose of 10 and 500 mg is administered, and the volume of distribution is 44 ml/kg, which is serum volume on average. 

Hortobagyi GN. 2005. Trastuzumab in the treatment of breast cancer. NEJM. 353 1734-1736. 

Dybdal N, Leiberman G, Anderson S, et al. Determination of HER2 gene amplification by fluorescence in situ hybridization and concordance with the clinical trials immunohistochemical assay in women with metastatic breast cancer evaluated for treatment with trastuzumab. Breast Cancer Res. Treat. 2005 93 3-11. 

Vogel CL, Cobleigh MA, Tripathy D, et al. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J. Clin. Oncol. 2002 20 719-726. 

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