Seminars in oncology
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Seminars in oncology · Dec 2000
ReviewChemotherapy sensitization by rituximab: experimental and clinical evidence.
For most lymphomas, chemotherapy is palliative because of an inability to overcome drug resistance within the lymphoma cells and attempts at overcoming specific drug resistance mechanisms, such as multidrug resistance, have had limited success. However, accumulating evidence suggests that the ability to activate apoptotic pathways may be an important determinant of chemotherapy sensitivity and presents a potentially important new therapeutic strategy. Studies have shown that distinct cellular thresholds exist for apoptosis, and it is likely that multiple developmental and environmental factors converge in a dynamic process to regulate this set point. ⋯ Monoclonal antibodies against the CD20 receptor have been shown to directly induce apoptosis and may serve to modulate the threshold for chemotherapy-induced apoptosis. Recent clinical studies of the monoclonal antibody, rituximab (Rituxan; Genentech, Inc, South San Francisco, CA and IDEC Pharmaceutical Corporation, San Diego, CA), and combination chemotherapy have produced unexpectedly high rates of response and progression-free survival, suggesting rituximab improves the efficacy of chemotherapy. Taken together, the results from in vitro and clinical studies suggest that rituximab may modulate the sensitivity of B-cell lymphomas to chemotherapy.
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Seminars in oncology · Dec 2000
Multicenter Study Clinical TrialRituximab as first-line systemic therapy for patients with low-grade lymphoma.
Rituximab (Rituxan; Genentech, Inc, South San Francisco, CA and IDEC Pharmaceutical Corporation, San Diego, CA), the first monoclonal antibody available for the systemic treatment of cancer, yields a 48% response rate in patients with refractory low-grade non-Hodgkin's lymphoma. This preliminary report describes the use of rituximab, instead of standard chemotherapy, in 39 previously untreated patients with stages II-IV low-grade non-Hodgkin's lymphoma All patients received rituximab 375 mg/m2 by intravenous infusion for 4 consecutive weeks and were evaluated for response at week 6. Patients with stable disease or an objective response received repeat 4-week courses at 6-month intervals, for a maximum of four treatment cycles. ⋯ Treatment was well tolerated. The high level of activity suggests that initial treatment with rituximab is a reasonable option in this group of patients, and that repeat maintenance courses at 6-month intervals are feasible and well tolerated. Further follow-up evaluation is necessary to determine the merits of this approach compared with traditional chemotherapeutic treatment.
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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.
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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.