Seminars in oncology
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Seminars in oncology · Dec 2000
ReviewOverview of idiopathic thrombocytopenic purpura: new approach to refractory patients.
Idiopathic thrombocytopenic purpura is a disorder in which autoantibodies are made to platelets, resulting in accelerated platelet destruction. The diagnosis may be made in outpatients who are previously well or in patients with multiple medical conditions and medications. There are no unequivocal ways to distinguish immune thrombocytopenias from other thrombocytopenias, even with state-of-the-art tests including anti-platelet antibodies, thrombopoietin, glycocalicin, and platelet reticulocyte counts. ⋯ Treatment of idiopathic thrombocytopenic purpura should be individualized. Substantial platelet increases are seen in more than 50% of patients who receive intravenous IgG, intravenous anti-D, steroids, or splenectomy. Two additional agents showing promising clinical trial experience are anti-CD40 ligand and rituximab (Rituxan; Genentech, Inc, South San Francisco, CA and IDEC Pharmaceutical Corporation, San Diego, CA).
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The HER2 gene (also known as neu and as c-erb-B2) encodes a 185-kd transmembrane glycoprotein receptor with intrinsic tyrosine kinase activity. HER2 is overexpressed in 25% to 30% of human breast cancers, plays a role in the pathogenesis of breast cancer, and predicts for a worse prognosis in patients with metastatic disease. Trastuzumab (Herceptin; Genentech, Inc, So. ⋯ The most clinically significant adverse event has been cardiac dysfunction syndrome, which occurred in less than 5% of patients. Trastuzumab is not associated with the other commonly observed side effects of chemotherapy, such as alopecia, mucositis, and neutropenia. The results from these studies demonstrate that trastuzumab is active and safe in patients with metastatic HER2-overexpressing breast cancer.
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Several recent advances have led to accelerated progress in breast cancer therapy. The development of new drugs with novel mechanisms of action, such as the taxanes, or oral bioavailability, such as capecitabine, has expanded the horizons of available chemotherapy. ⋯ San Francisco, CA) represents an exciting new direction that opens doors to new concepts in antitumor therapy. This report will review the most exciting possibilities for expanding the field of breast cancer management.
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Seminars in oncology · Oct 2000
ReviewImmunotherapeutic strategies for the treatment of plasma cell malignancies.
The use of immunotherapy to treat patients with plasma cell dyscrasias (PCD) such as multiple myeloma (MM) and Waldenström's macroglobulinemia (WM) has gained enormous interest in recent years, with considerable efforts being mounted by many investigators. These efforts have included the use of serotherapy (antibody-mediated immunotherapy), vaccination strategies aimed at inducing allogeneic as well as autologous anti-MM immunity, and the use of donor lymphocyte infusions (DLIs). A number of cell surface antigens on malignant plasma cells and/or B cells in MM and/or WM patients have been proposed for use in tumor cell-targeted serotherapy, including immunoglobulin idiotype, CD19, CD20, CD38, CD54, CD138, HM1.24, and MUC1 core protein. ⋯ In addition, proposed immunization strategies aimed at inducing autologous immunity include vaccination with dendritic cells pulsed with MM antigens, MM cell-dendritic cell fusions, carrier-linked idiotype protein, catalytic subunit of telomerase, or DNA encoding for single-chain variable fragments (scFv) linked to a carrier protein gene. Whole tumor vaccination strategies are also being examined and include the use of MM cells transfected and/or stimulated with cytokines, costimulatory molecules, or CD40 ligand. Finally, potential obstacles to the use of immunotherapy, including the presence of resistance antigens on MM and WM tumor cells, are discussed.
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Seminars in oncology · Oct 2000
ReviewCurrent and planned clinical trials with trastuzumab (Herceptin).
Trastuzumab (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. ⋯ 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.