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Phase I dose escalation study of vinorelbine and topotecan combination chemotherapy in patients with recurrent lung cancer

机译:长春瑞滨联合拓扑替康联合化疗治疗复发性肺癌的第一阶段剂量递增研究

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摘要

BackgroundA platinum doublet is the current standard treatment for good performance status patients with advanced non-small cell lung cancer (NSCLC) and extensive stage small cell lung cancer (SCLC) with good performance status. However, platinum-based treatment may be associated with significant toxicities, therefore alternative platinum-free combinations should be investigated. Topotecan is a topoisomerase I inhibitor that exerts its cytotoxic effect through stabilization of the topoisomerase I-DNA complex. Preclinical data suggests synergy between topoisomerase I inhibitors and mitotic spindle poisons. Considerable hematologic toxicities have been reported with topotecan dosed for 5 consecutive days in combination with vinorelbine. Therefore, the aim of this study was to evaluate the optimal dosage and the maximal tolerated dose (MTD) of topotecan and vinorelbine in patients with relapsed or refractory non-small cell or small cell lung cancer administered on an alternate dosing schedule.
机译:背景技术铂双线药物是目前状态良好的晚期非小细胞肺癌(NSCLC)和广泛阶段小细胞肺癌(SCLC)表现良好状态患者的标准治疗方法。但是,基于铂的治疗可能会伴有明显的毒性,因此应研究其他无铂组合。拓扑替康是一种拓扑异构酶I抑制剂,可通过稳定拓扑异构酶I-DNA复合物发挥其细胞毒性作用。临床前数据表明,拓扑异构酶I抑制剂与有丝分裂纺锤体中毒之间具有协同作用。托泊替康连续5天与长春瑞滨合用时,已报告了相当大的血液学毒性。因此,本研究的目的是评估在交替给药方案下复发或难治的非小细胞或小细胞肺癌患者中拓扑替康和长春瑞滨的最佳剂量和最大耐受剂量(MTD)。

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