Seminars in oncology
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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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Rituximab (Rituxan; Genentech, Inc, South San Francisco, CA and IDEC Pharmaceutical Corporation, San Diego, CA) is a unique monoclonal antibody for the treatment of non-Hodgkin's lymphoma. This chimeric mouse/human antibody was discovered in 1991 at IDEC Pharmaceuticals' laboratories, where the antibody was genetically engineered and produced utilizing high-yield expression systems. It is a human IgG1 kappa antibody with mouse variable regions isolated from a murine anti-CD20 antibody, IDEC-2B8, that binds with high affinity to cells expressing the CD20 antigen found on the surface of malignant and normal B cells, but not on other normal tissues. ⋯ Substantial research has been performed over the past 8 years to further the understanding of this novel therapeutic. Nevertheless, much remains to be accomplished in key areas such as mechanism of action and resistance, combinations with chemotherapy, biologics and radiotherapy/radioimmunotherapy, role within multimodality regimens, and nonmalignant applications. Research conducted in the coming years should be targeted toward resolving these important issues.
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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
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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HER-2 (c-erbB-2, neu) is an important prognostic and predictive factor in breast cancer. Clinical trials utilizing a humanized version of the anti-HER-2 murine monoclonal antibody 4DS, trastuzumab (Herceptin; Genentech Inc, South San Francisco, CA), have shown antitumor activity in patients with HER-2-positive metastatic breast cancer. ⋯ The Breast Cancer Intergroup has recently completed several trials evaluating new chemotherapy treatment approaches for patients with node-positive breast cancer, which form the basis for several ongoing and planned clinical trials incorporating trastuzumab. These clinical trials and the evolving role of trastuzumab-containing adjuvant systemic therapy for breast cancer will be reviewed.