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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Seminars in oncology · Jun 2002
ReviewTrastuzumab/chemotherapy combinations in metastatic breast cancer.
The past decade has seen many advances in the treatment of advanced breast cancer, including the development of both new chemotherapy drugs and novel targeted agents. Trastuzumab, a humanized monoclonal antibody directed against the HER2/neu protein, has been shown to be an efficacious treatment for HER2-overexpressing metastatic breast cancer, both as a single agent and when used in combination with chemotherapy. ⋯ Further trials are currently underway evaluating the use of trastuzumab in combination with other forms of chemotherapy, including vinorelbine, docetaxel, anthracyclines, and platinum agents. Hopefully, information from these trials will help resolve questions regarding the efficacy of various combinations and dosing schedules so that trastuzumab may be used most effectively in the treatment of HER2-overexpressing breast cancer in both the metastatic and the adjuvant settings.
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Seminars in oncology · Jun 2002
ReviewTherapeutic options for essential thrombocythemia and polycythemia vera.
Several options exist for treating essential thrombocythemia and polycythemia vera. One approach is to assign the patient to a risk category from which treatment recommendations follow. The principal risks of essential thrombocythemia include thrombosis, major hemorrhage, and conversion to leukemia or myelofibrosis. ⋯ Anagrelide can be used with phlebotomy in selected patients. Women of childbearing age who are in the low-risk or intermediate-risk group can be treated with phlebotomy alone and low-dose aspirin if the platelet count is < 1,500 x 10(9)/L. For high-risk patients or pregnant patients, IFN-alpha can be added.
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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.