Seminars in oncology
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Seminars in oncology · Jun 2002
ReviewDocetaxel in the treatment of breast cancer: an update on recent studies.
Recently there has been great interest in developing combination regimens involving taxanes and anthracyclines for the treatment of advanced breast cancer. Docetaxel in particular has substantial activity when combined with doxorubicin. In one randomized trial, the combination of doxorubicin 50 mg/m(2) and docetaxel 75 mg/m(2) showed significantly greater activity than doxorubicin plus cyclophosphamide (AC), producing a higher response rate (60% v 47%) and longer time to progression. ⋯ The TAC and doxorubicin/docetaxel regimens have been compared with non-docetaxel-containing programs in randomized adjuvant trials which have completed accrual but are not yet mature. A second generation of adjuvant trials compares sequential versus synchronous docetaxel-based polychemotherapy. In addition, based on preclinical data suggesting a synergistic interaction between docetaxel, platinum salts, and trastuzumab, as well as preliminary data from pilot studies in patients with HER2-positive metastatic disease showing tolerability and activity, adjuvant studies of this novel three-agent combination are in progress in patients with HER2-positive early breast cancer.
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Seminars in oncology · Jun 2002
ReviewTrastuzumab cardiotoxicity: Speculations regarding pathophysiology and targets for further study.
Trastuzumab, a monoclonal antibody that is selective for cells that overexpress the erbB2 receptor protein tyrosine kinase, is a promising targeted therapy for the treatment of breast cancer. Surprisingly, toxic cardiovascular side effects were discovered in late-phase clinical trials, and these effects were most prominent when trastuzumab was combined with anthracycline chemotherapy. ⋯ Further investigation of the role of normal and aberrant erbB2 signaling in the development of cardiac dysfunction could lead to an improved understanding of the pathophysiology of cardiac dysfunction and may lead to novel therapies for the treatment of heart failure, regardless of etiology. Understanding the nature and specificity of trastuzumab's cardiotoxic effects is important in better defining clinical criteria for inclusion and exclusion of patients who can safely receive trastuzumab for the treatment of breast cancer, or possibly other malignancies.
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Gemcitabine has become a new standard for treatment of advanced pancreatic cancer. This development is based not only on drug efficacy but also on a favorable side-effect profile. Combinations of gemcitabine with antitumor drugs such as cisplatin, 5-fluorouracil, docetaxel, irinotecan, oxaliplatin, or capecitabine, and biological agents such as cetuximab or trastuzumab, have yielded promising results in phase II trials. However, none of these combinations has yet reached the level of an evidence-based standard treatment.
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Monoclonal antibodies have been used as therapeutic agents for many years. In 1997, rituximab (Rituxan; Genentech, Inc, South San Francisco, CA, and IDEC Pharmaceuticals, San Diego, CA) became the first monoclonal antibody to be approved by the US Food and Drug Administration for a cancer indication. The use of rituximab in the treatment of low-grade or follicular, relapsed, or refractory CD20-positive B-cell non-Hodgkin's lymphoma was approved in November 1997 for United States marketing under the trade name Rituxan. ⋯ A significant amount of clinical research has been performed over the past 9 years, which has served to further our understanding of the potential clinical applications for this novel therapeutic agent. Ongoing and future clinical trials are reviewed in this article. However, much remains to be accomplished in key areas such as combinations with chemotherapy, biologics (including other antibodies), and radiotherapy/radioimmunotherapy; its role within multimodality regimens; and other malignant (beyond low-grade non-Hodgkin's lymphoma) and nonmalignant applications.
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Seminars in oncology · Feb 2002
Multicenter Study Clinical TrialThe role of rituximab and chemotherapy in aggressive B-cell lymphoma: a preliminary report of dose-adjusted EPOCH-R.
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. Monoclonal antibodies against the CD20 antigen directly induce apoptosis and may serve to modulate the threshold for chemotherapy-induced apoptosis. Rituximab (Rituxan; Genentech, Inc, South San Francisco, CA, and IDEC Pharmaceuticals, San Diego, CA), a monoclonal antibody against CD20, was combined with dose-adjusted EPOCH (infusional etoposide/vincristine/doxorubicin/bolus cyclophosphamide/prednisone) chemotherapy and tested in 38 untreated or relapsed poor-prognosis aggressive lymphomas. ⋯ Complete remissions were achieved in 85% and 64% of untreated and previously treated patients, respectively; additionally 42% of patients with disease refractory before therapy achieved complete remission. At a median follow-up of 12 months, progression-free and overall survival in the previously untreated group was 85% and 79%, respectively, and no patient in complete remission has relapsed. These results suggest that rituximab may modulate the sensitivity of B-cell lymphomas to chemotherapy.