Seminars in oncology
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Metastasis to the CNS develops in nearly half of patients with advanced melanoma; in 15% to 20% of these patients, the CNS is the first site of relapse. While systemic therapy for metastatic melanoma produces objective responses in 15% to 50% of patients, the available drugs do not penetrate well into the CNS, and these patients rarely benefit from systemic therapy. Although brain metastasis may be treated with surgery and/or stereotactic radiosurgery (SRS) when disease is limited to approximately one to three lesions, treatment for patients with large or multiple metastases is limited to whole brain irradiation (WBRT). ⋯ Temozolomide (TMZ) is an oral alkylating agent that acts via the same mechanism as dacarbazine (DTIC), the most active single agent in melanoma. TMZ, which is highly active in brain tumors, has also been associated with activity in systemic and CNS metastases in melanoma patients, also in the 25% range. Efforts are underway to assess the additive benefit of TMZ and other drugs to WBRT or focused radiotherapy in this disease.
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Seminars in oncology · Aug 2002
Case ReportsBendamustine in the treatment of chronic lymphocytic leukemia: results and future perspectives.
Chronic lymphocytic leukemia (CLL) occurs predominantly in elderly patients. The treatment options for patients with CLL have increased with the introduction of purine analogs, and promising results have been reported with fludarabine and cladribine when these agents are used in newly diagnosed and relapsed disease. Monoclonal antibodies such as alemtuzumab and rituximab are also clinically active in CLL. ⋯ Bendamustine 100 mg/m(2) (days 1 and 2) was found to be an effective treatment for older patients with advanced CLL, with 14 of 21 patients responding. Complete hematologic remission was achieved in six of 21 patients and a further eight patients achieved a partial hematologic remission. The main toxicities were hematologic; nonhematologic side effects were mild and uncommon.
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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.