Weekly paclitaxel with intermittent imatinib mesylate (Gleevec): tolerance and activity in recurrent epithelial ovarian cancer.

作者: Amy Tiersten , Bhavana Pothuri , Lucia Borgato , Stephanie Blank , Leslie Boyd

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摘要: Objective: Imatinib mesylate (IM, Gleevec), a potent PDGF/PDGFR tyrosine kinase inhibitor, affects stroma and vascular endothelial cells. Our study sought to determine the safety activity of paclitaxel with an intermittent schedule IM. Materials Methods: rEOC patients previously treated platinum/paclitaxel ≤2 regimens for recurrence were enrolled. Paclitaxel 80 mg/m 2 was given on days 3, 10, 17 every 28 oral IM 300 mg bid 1-4, 8-11, 13-18. Results: Between 2007- 2009, 14 enrolled, 12 evaluable. Nine at weeks. Objective responses (by RECIST and/or CA125) occurred in 4 patients. There no grade 4, only four 3 toxic events: diarrhea, edema cases neutropenia. Early closure due sufficient information preliminary encouraging efficacy results. Conclusion: This weekly regimen is tolerable anti-tumor activity, making it suitable as part future studies. Most epithelial ovarian cancer (EOC) will relapse undergo treatment 'second-line' drugs, such taxanes, topotecan, pegylated liposomal doxorubicin gemcitabine (1). Greater understanding mechanisms action resistance pathways these drugs may lead more long-term control disease. Weekly administration provides pharmaco- logically-based continuous exposure that effective less than three weeks (2-3). Inhibition angiogenesis contribute antitumor effects beyond direct cytotoxicity (4-6). Gleevec ® ), 2-phenylamino- pyrimidine derivative, selective inhibitor ABL, c-KIT, platelet-derived growth factor receptor (PDGFR) kinases (7). Platelet-derived (PDGF)

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