Clin Cancer Res
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Somatic mutations in the epidermal growth factor receptor (EGFR) have been identified in patients with advanced non-small cell lung cancer who achieve dramatic clinical and radiographic response to the EGFR tyrosine kinase inhibitors (TKI) gefitinib and erlotinib. These mutations in EGFR are found more frequently in patients with adenocarcinomas, nonsmokers, patients of Asian ethnicity, and in females: the same populations that are the most likely to have a clinical response when treated with EGFR TKIs. ⋯ These findings suggest that for patients with advanced non-small cell lung cancer bearing EGFR mutations, treatment with an EGFR TKI should be incorporated as at least part of their initial therapy. These approaches are being studied in ongoing clinical trials and will spur the development of additional technology for EGFR mutation detection.
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Elevated proportions of regulatory T cells (T(reg)) are present in patients with a variety of cancers, including malignant glioma, yet recapitulative murine models are wanting. We therefore examined T(regs) in mice bearing malignant glioma and evaluated anti-CD25 as an immunotherapeutic adjunct. ⋯ Systemic anti-CD25 administration does not entirely eliminate T(regs) but does prevent T(reg) function. This leads to safe enhancement of tumor immunity in a murine glioma model that recapitulates the tumor-induced changes to the CD4 and T(reg) compartments seen in patients with malignant glioma.
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Bevacizumab is a recombinant, humanized monoclonal antibody against vascular endothelial growth factor. Erlotinib HCl is a reversible, highly selective epidermal growth factor receptor tyrosine kinase inhibitor. Additionally, both agents have shown benefit in patients with previously treated non-small cell lung cancer (NSCLC). ⋯ The median overall survival for the 34 patients treated at the phase II dose was 12.6 months, with progression-free survival of 6.2 months. Encouraging antitumor activity and safety of erlotinib plus bevacizumab support further development of this combination for patients with advanced NSCLC. A randomized phase II trial has been completed, and a phase III trial is ongoing.
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This phase II study was undertaken to assess objective response and toxicity of histone deacetylase inhibitor depsipeptide in patients with neuroendocrine tumors. ⋯ Depsipeptide was associated with a high number of potentially serious cardiac adverse events in patients with metastatic neuroendocrine tumor. As sudden death possibly associated with depsipeptide was observed in this trial, the risks for potentially life-threatening arrhythmia associated with this agent need to be comprehensively evaluated.
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Somatic mutations in the epidermal growth factor receptor (EGFR) have been detected in patients with non-small cell lung cancer (NSCLC) and are associated with sensitivity to treatment with gefitinib or erlotinib. Our study explored the relationship between the two most common types of somatic EGFR mutations, exon 19 deletions and the L858R point mutation, and outcomes of patients following treatment with gefitinib or erlotinib. ⋯ Patients with NSCLC and EGFR exon 19 deletions have a longer survival following treatment with gefitinib or erlotinib compared with those with the L858R mutation. Pooling of greater numbers of patients and completion of prospective trials are needed to further define the predictive and prognostic roles of different EGFR mutations with respect to treatment with gefitinib, erlotinib, and other EGFR inhibitors.