Herceptin metastatic breast cancer

Vogel, C.L., et al., "First-line Herceptin Monotherapy in Metastatic Breast Cancer," Oncology, 61 Suppl S2, 37-42 (2001). 

Trastuzumab Herceptin Humanized IgGltc anti-HER2 HER2 overexpressing metastatic breast cancer 1998 United States... 

Trastuzumab Herceptin Genentech-Roche Metastatic breast cancer... 

Baselga, J., D. Tripathy, J. Mendelsohn, S. Baughman, C. C. Benz, L. Dantis, N. T. Sklarin, A. D. Seidman, C. A. Hudis, J. Moore, P. P. Rosen, T. Twaddell, I. C. Henderson, and L. Norton. Phase II study of weekly intravenous trastuzumab (Herceptin) in patients with HER2/neu-overexpressing metastatic breast cancer. Semin Oncol. 26 78-83.1999. 

Vogel C, Cobleigh MA, Tripathy D, et al. First-line, single-agent Herceptin(R) (trastuzumab) in metastatic breast cancer, a preliminary report. Eur J Cancer 2001 37(Suppl 1 ) 25—29. 

Burstein HJ, Kuter I, Richardson PG. Herceptin and Vinorelbine for HER-2 positive metastatic breast cancer a phase II study. Proc Am Soc Clin Oncol 2000 19 102 (abstr). 

F. Role in therapy In untreated HER2-overexpressing metastatic breast cancer, the addition of Herceptin to paclitaxel increases response rates and time to progression it... 

G. Other applications Herceptin has been combined with cisplatin in the treatment of heavily pretreated metastatic breast cancer. Treatment of patients with ovarian cancer is under investigation. A recent study demonstrated that Herceptin increased the clinical benefits of first-line chemotherapy—doxorubicin (or epiru-bicin) and cyclophosphamide or pacli-taxel—in metastatic breast cancer that overexpressed HER2. 

The data on Herceptin—alone or in combination with current chemotherapies for metastatic breast cancer—clearly demonstrate that the degree of HER2 overexpression is related to treatment response. Inhibition of this tumor-transforming growth factor has proved to produce clinical effects but only in those patients with overexpressed phenotypes (2 and 30-These results formed the basis for the requirement to determine levels of HER2 on tumor tissues before deciding whether Herceptin is the best treatment strategy for an individual patient. 

Phase 1 clinical trials demonstrated that Herceptin is safe and confined to the tumor. However, phase 2 trials indicated that the efficacy of the antibody is superior when given with chemotherapy (Pegram et al., 1998). Phase 3 trials have indicated that Herceptin, when added to conventional chemotherapy, can benefit patients with metastatic breast cancer that overexpresses HER-2, prolonging relapse and overall survival (Slamon et al., 2001). Similarly, extensive studies by Menden et al. (2001) support the weekly Docetaxel... 

Vogel, C. L., Cobleigh, M. A., Tripathy, D., Harris, L., Fehrenbacher, L., Slamon, D., Ash, M., Novotny, W., and Shak, S. (1998). Efficacy and safety of Herceptin (Trastuzumab, humanized anti-HER-2 antibody) as a single agent in first-line treatment of HER-2 overexpressing metastatic breast cancer (HER-2+/MBC). Breast Cancer Res. Treat. 50, 232a. 

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. ... 

Herceptin Trastuzumab Genentech 9/1998 Metastatic breast cancer CHO... 

Trastuzumab Herceptin (Genentech) Metastatic breast cancer (Her2neu-I-)... 

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. 

Slamon D, Leyland-Jones B, Shak S, Paton V, Bajamonde A, Flemiong T, Eirmann W, Wolter J, Baselga J, Norton L. Addition of Herceptin (humanized anti-HER2 antibody) to first line chemotherapy for HER2 overexpressing metastatic breast cancer (HER2-I-/MBC) markedly increases anticancer activity a randomised, multinational, controlled phase III trial (Abstract 377). Proc Am Soc Clin Oncol 1998 17 98a. 

Suter TM, Cook-Brunsb, Bartonc C. Cardiotoxicity associated with trastuzumab (Herceptin) therapy in the treatment of metastatic breast cancer. The Breast. 2004 13(3) 173-183. 

Trade name Herceptin (Genentech) Indications Metastatic breast cancer Category Antineoplastic HER2 antagonist Half-life 5.8 days... 

The fourth broad use of a test result is concerned with patient management. In a patient with a chronic disease, the result may be used to select the type of intervention and assess the effectiveness of an intervention, and the action will be to change or continue the treatment. In women with metastatic breast cancer, the HER-2/ e status is used to assess the potential usefulness of Herceptin therapy. In a person with diabetes, hemoglobin (Hb) Ai measurements are used to assess glyceraic control and thus the effectiveness of therapy. 

Extra JM, Cognetti F, Chan S, et al. First-hne trastuzumab (Herceptin) plus docetaxel versus docetaxel alone in women with HER2-positive metastatic breast cancer (MBC) Results from a randomized phase II trial (M77001) (Meeting abstract). San Antonio Breast Cancer Symposium 2003 A217. 

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