Seminars in oncology
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Seminars in oncology · Feb 2003
Review Randomized Controlled Trial Clinical TrialDose-comparative monotherapy trials of ZD1839 in previously treated non-small cell lung cancer patients.
Patients with non-small cell lung cancer (NSCLC) frequently present, or relapse, with unresectable disease that is resistant to standard chemotherapy. There is, therefore, an urgent need for new treatments for NSCLC and other solid tumors. ZD1839 (Iressa; AstraZeneca Pharmaceuticals LP, Wilmington, DE), an orally active, selective epidermal growth factor receptor-tyrosine kinase inhibitor, has shown promising antitumor responses in phase I clinical trials in heavily pretreated patients with advanced NSCLC and other solid tumors. ⋯ Symptom improvement rates (increase of at least two points on the Lung Cancer Subscale) were 43% and 35%, respectively. Both doses of ZD1839 were well tolerated in this trial. The results of IDEAL-1 and IDEAL-2 indicate that ZD1839 monotherapy may offer a single-agent alternative for patients with advanced solid tumors who have received and progressed on prior chemotherapy, many of whom have exhausted their therapy options.
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Seminars in oncology · Feb 2003
ReviewFirst-line and maintenance treatment with rituximab for patients with indolent non-Hodgkin's lymphoma.
The chimeric human-mouse anti-CD20 monoclonal antibody rituximab has durable single-agent activity in patients with relapsed and refractory indolent non-Hodgkin's lymphoma. The focus of this report is a phase II trial evaluating the efficacy of single-agent rituximab as first-line therapy in patients with indolent lymphoma and scheduled maintenance treatment in prolonging duration of remission. Patients received a 4-week course of standard rituximab (375 mg/m(2) intravenously weekly x 4). ⋯ In summary, rituximab appears highly active as first-line single-agent therapy for indolent non-Hodgkin's lymphoma and responses may be improved with maintenance courses of rituximab. Results suggest a higher response rate to rituximab when used as first-line compared with second/third-line treatment, particularly in the subset of patients with SLL and chronic lymphocytic leukemia. Further follow-up will provide important information regarding the impact of first-line and maintenance rituximab on progression-free survival in patients with indolent non-Hodgkin's lymphoma.
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CNS involvement is a common feature of metastatic melanoma. Despite this, there is little evidence upon which clinicians can base decisions about treatment. The short prognosis and significant symptoms usually associated with melanoma brain metastases have excluded these patients from clinical trials. In Europe the standard treatment involves whole brain radiotherapy, although selected centers offer other modalities, including surgery, radiosurgery, and chemotherapy.
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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 · 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.