Seminars in oncology
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Seminars in oncology · Feb 2001
ReviewRationale for trastuzumab (Herceptin) in adjuvant breast cancer trials.
The discovery of the HER2/neu proto-oncogene and its role in the pathogenesis of breast cancer tumors, and the development of the anti-HER2 monoclonal antibody, trastuzumab (Herceptin; Genentech, South San Francisco, CA), directed against the HER2 receptor represent major milestones in the research developments in breast cancer, making trastuzumab the first monoclonal antibody available for treatment of this disease. Clinical trials in HER2-positive patients have demonstrated that the combined use of targeted therapy with trastuzumab in conjunction with cytotoxic chemotherapy is associated with improved time to disease progression and overall survival. Unfortunately, findings also demonstrate an increased risk for cardiotoxicity when trastuzumab is combined with anthracyclines. ⋯ The adjuvant trial design for the Breast Cancer International Research Group uses a control arm of doxorubicin/cyclophosphamide for four cycles followed by docetaxel for four cycles and the second arm contains the addition of trastuzumab to the taxane sequence. The third arm, a non-anthracycline-containing regimen, contains docetaxel, a platinum agent (either cisplatin or carboplatin), and trastuzumab. The rationale for the selection of this three-drug regimen is based on the biology of the system and preclinical and clinical findings that demonstrate a high potential for clinical synergy.
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Seminars in oncology · Dec 2000
ReviewThe role of HER-2 expression in predicting response to therapy in breast cancer.
HER-2 expression may have predictive value regarding response to therapeutic interventions in breast cancer. A number of reports describe the interaction of HER-2 overexpression and tamoxifen, but data are inconclusive. ⋯ The Clinical Trials Assay, a scoring system for tumor material, has been used successfully in the trastuzumab clinical development program. As many of the early studies evaluating the role of HER-2 were retrospective, controlled prospective studies are needed to best determine the value of trastuzumab in the adjuvant clinical setting.
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Seminars in oncology · Dec 2000
ReviewOptimizing the use of rituximab for treatment of B-cell non-Hodgkin's lymphoma: a benefit-risk update.
Rituximab (Rituxan; Genentech, Inc, South San Francisco, CA and IDEC Pharmaceutical Corporation, San Diego, CA), the first monoclonal antibody approved in the United States for the treatment of cancer, is indicated for the treatment of patients with relapsed or refractory CD20+ low-grade non-Hodgkin's lymphoma. From November 1997 through May 1999, approximately 36,000 patients have been treated with rituximab. Serious cardiopulmonary infusion reactions culminating in death have been reported to occur in approximately 0.04% to 0.07% of patients. ⋯ Serious infusion-related adverse drug reactions, most often consisting of cardiopulmonary reactions associated with the rapid lysis of large numbers of circulating malignant cells, have been fatal in approximately 0.5 per 1,000 treated patients. Major risk factors include high numbers of circulating malignant lymphoma cells, pulmonary infiltrates or lymphoma involvement, and prior cardiovascular disease. This report updates the safety experience of rituximab therapy with data from clinical trials and postmarketing safety experience, and examines how this information can be used to optimize therapy.
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Seminars in oncology · Dec 2000
ReviewHER-2/neu as a therapeutic target in non-small cell lung cancer, prostate cancer, and ovarian cancer.
HER-2/neu is overexpressed in most epithelial malignancies. Lung cancer, prostate cancer, and ovarian cancer are common epithelial tumors in which clinical trials are currently in progress to explore the potential therapeutic role for monoclonal antibodies to HER-2/neu (trastuzumab [Herceptin; Genentech, Inc, South San Francisco, CA]). In preclinical studies with tumor cell lines, trastuzumab was found to have additive and synergistic effects with some chemotherapeutic agents. Clinical trials investigating combination chemotherapy with trastuzumab and a variety of chemotherapeutic agents are already in progress in lung cancer.
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Seminars in oncology · Dec 2000
ReviewThe use of rituximab in the treatment of malignant and nonmalignant plasma cell disorders.
CD20 is a B-cell-restricted antigen that, for the most part, is expressed from the pre-B-cell to the mature B-cell stage of B-cell differentiation. Several transcription factors regulate CD20 expression during B-cell differentiation, the most important of which appear to be PU.1 and Pip (PU.1 interacting protein). As B cells differentiate to plasma cells, CD20 expression is down-regulated, which coincides with PU.1 downregulation in plasma cells. ⋯ CD20 also is expressed on subpopulations of normal donor plasma cells, which may include autoantibody-secreting plasmacytes. In view of these findings, the anti-CD20 chimeric monoclonal antibody, rituximab (Rituxan; Genentech, Inc, South San Francisco, CA and IDEC Pharmaceutical Corporation, San Diego, CA), has been evaluated in the treatment of Waldenstrom's macroglobulinemia and multiple myeloma, as well as in nonmalignant plasma cell disorders including IgM polyneuropathies, immune thrombocytopenias, and autoimmune hemolytic anemias, with reported activity in these entities. An update of these clinical efforts is presented in this report.