Seminars in oncology
-
The CD20 antigen is an attractive target for antibody-directed therapy due to its stable, high-level surface expression on normal and malignant B cells. Rituximab (Rituxan; IDEC Pharmaceuticals, San Diego, and Genentech, Inc, San Francisco, CA) is an anti-CD20 chimeric monoclonal antibody that has shown single-agent activity in phase I and II clinical trials in patients with B-cell non-Hodgkin's lymphoma. This antibody has a long serum half-life and low immunogenicity. ⋯ The mechanism of action likely includes both immune-mediated effects and direct effects. The generally mild toxicity profile and excellent single-agent activity provide the rationale for use with or following chemotherapy. Additional studies evaluating these and other combinations are under way.
-
Seminars in oncology · Oct 1999
Multicenter Study Clinical TrialRituximab in indolent lymphoma: the single-agent pivotal trial.
Rituximab (Rituxan; IDEC Pharmaceuticals, San Diego, CA, and Genentech, Inc, San Francisco, CA) is a chimeric anti-CD20 monoclonal antibody that targets mature B cells and most B-cell malignancies. Rituximab was the first monoclonal antibody to be approved for therapeutic use for any malignancy. ⋯ The overall results of the trial have been previously reported; additional aspects of the trial (eg, pharmacokinetics) have been reported separately as well. The current report includes an update, expansion, and synthesis of data from the single-agent pivotal trial of rituximab.
-
Seminars in oncology · Oct 1999
ReviewOverview of the clinical development of rituximab: first monoclonal antibody approved for the treatment of lymphoma.
Rituximab (Rituxan; IDEC Pharmaceuticals, San Diego, CA, and Genentech, Inc, San Francisco, CA) is a genetically engineered monoclonal antibody for the treatment of non-Hodgkin's lymphoma. This chimeric mouse/human, immunoglobulin GI kappa anti-CD20 antibody mediates complement-dependent cell lysis and antibody-dependent cellular cytotoxicity. It also has been shown to sensitize chemoresistant human lymphoma cell lines and to induce apoptosis. ⋯ Activity also has been seen in patients with bulky disease. Combination studies have been performed with interferon, cyclophosphamide/doxorubicin/vincristine/prednisone, and radioimmunotherapy. Rituximab, the first monoclonal antibody approved for the treatment of cancer, is safe and effective in treating patients with relapsed or refractory, CD-20 positive, B-cell, low-grade or follicular non-Hodgkin's lymphoma.
-
Patients with relapsed B-cell lymphomas are currently incurable with conventional doses of chemotherapy or radiotherapy. In recent years, new treatment options have become available for these patients, including the use of chimeric mouse-human anti-CD20 antibodies and radiolabeled anti-CD20 antibodies. ⋯ High-dose (131)I-anti-B1 antibody with stem cell transplantation generates objective responses in 85% to 90% of cases, including 75% to 80% complete remissions. Although more patients need to be evaluated with a longer follow-up period, radioimmunotherapy appears to be an effective and well-tolerated addition to the oncologists' armamentarium for relapsed lymphomas.
-
Seminars in oncology · Oct 1999
Multicenter Study Clinical TrialCHOP plus rituximab chemoimmunotherapy of indolent B-cell lymphoma.
Indolent (low-grade) B-cell lymphomas are responsive to single-agent and combination chemotherapy agents, but unfortunately possess an incurable, relapsing nature. Novel agents and innovative treatment approaches need to be evaluated in these patients, with the ultimate goals of maintaining good quality of life and prolonging overall survival. Novel combinations of chemotherapeutic agents, monoclonal antibodies (both unlabeled and radiolabeled), and anti-idiotypic vaccine therapies are currently being evaluated. ⋯ A 95% overall response (55%, complete remission; 40%, partial remission) rate using strict definitions for complete remission and extensive staging studies was achieved in a 40-patient intent-to-treat group. In addition, seven of seven patients with follicular histologies achieving complete remission also had clearing of BCL-2 (chromosome 14;18 translocation) positivity from blood and marrow by sensitive polymerase chain reaction assay, suggesting the eradication of subclinical minimal residual disease. Based on its single-agent efficacy, excellent toxicity profile, and ability to be successfully combined with combination chemotherapy (ie, CHOP), rituximab is currently undergoing extensive investigation in a large number of worldwide clinical trials to determine its optimal use in the treatment of CD20-positive neoplasms.