Seminars in oncology
-
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.
-
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.
-
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.
-
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.
-
Seminars in oncology · Dec 2000
ReviewTrastuzumab in combination with chemotherapy for the treatment of metastatic breast cancer.
Metastatic breast carcinoma still remains an incurable condition. The relentless search for novel agents that might prove useful for management has evolved toward monoclonal antibodies, in part because of a rapidly expanding understanding of breast cancer biology. Trastuzumab (Herceptin; Genentech, Inc, South San Francisco, CA) is a recombinant humanized monoclonal antibody against the HER-2 receptor that has shown antitumor activity as a single agent in phase I and II trials of patients with metastatic breast cancer overexpressing HER-2. ⋯ Two trials were presented at the 1999 meeting of the American Society of Clinical Oncology that evaluated this combination. One multicenter phase III trial showed clinical benefit and increased survival for patients with HER-2-overexpressing metastatic breast cancer treated with chemotherapy plus trastuzumab. A phase II trial, reviewed in this report, evaluated the efficacy and safety of weekly paclitaxel plus trastuzumab for patients with metastatic breast carcinoma, including those overexpressing and nonoverexpressing HER-2.