Clin Cancer Res
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Gefitinib and erlotinib can penetrate into the central nervous system (CNS) and elicit responses in patients with brain metastases (BM) from non-small cell lung cancer (NSCLC). However, there are incomplete data about their impact on the development and control of CNS metastases. ⋯ Our data suggest a lower risk of CNS progression in patients with advanced NSCLC and somatic EGFR mutations initially treated with gefitinib or erlotinib than published rates of 40% in historical series of advanced NSCLC patients. Further research is needed to distinguish between the underlying rates of developing CNS metastases between NSCLC with and without EGFR mutations and the impact of gefitinib and erlotinib versus chemotherapy on CNS failure patterns in these patients.
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To assess the clinical and biological activity of the association of bevacizumab and fotemustine as first-line treatment in advanced melanoma patients. ⋯ The combination of bevacizumab plus fotemustine has clinical activity in advanced melanoma and promotes systemic modulation of angiogenesis and lymphangiogenesis factors.
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Brain metastases of breast cancer appear to be increasing in incidence, confer significant morbidity, and threaten to compromise gains made in systemic chemotherapy. The blood-tumor barrier (BTB) is compromised in many brain metastases; however, the extent to which this influences chemotherapeutic delivery and efficacy is unknown. Herein, we answer this question by measuring BTB passive integrity, chemotherapeutic drug uptake, and anticancer efficacy in vivo in two breast cancer models that metastasize preferentially to brain. ⋯ This work shows that the BTB remains a significant impediment to standard chemotherapeutic delivery and efficacy in experimental brain metastases of breast cancer. New brain permeable drugs will be needed. Evidence is presented for vascular remodeling in BTB permeability alterations.
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Systemic therapies for breast cancer brain metastasis are largely unsuccessful. Mouse models of brain metastasis show significant heterogeneity in uptake of paclitaxel and doxorubicin, with average levels more than those seen in normal brain tissue, but significantly less than in metastases to other organs.
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Cancer cell survival, invasion, and metastasis depend on cancer cell proliferation and on tumor-induced angiogenesis. We evaluated the efficacy of the combination of sorafenib and erlotinib or cetuximab. ⋯ Combination treatment with sorafenib and erlotinib or cetuximab has synergistic antitumor effects in human colorectal and lung cancer cells.