TOPOTECAN & ETOPOSIDE IN ADVANCE NON SMALL CELL LUNG CANCER

拓扑替康

• 批准号: 5219172
• 负责人: NATHAN LEVITAN
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5219172
• 关键词: DNA topoisomerases; biopsy; clinical research; clinical trial phase I; dosage; drug adverse effect; drug screening /evaluation; enzyme activity; etoposide; human therapy evaluation; neoplasm /cancer chemotherapy; nonsmall cell lung cancer; pharmacokinetics; topotecan

This protocol utilizes a dose intense chemotherapy treatment regimen which takes advantage of the synergistic activity between inhibitors of topoisomerase I and II. This is a phase I/II clinical trial for patients with advanced non-small cell lung cancer who have not received prior chemotherapy. We hypothesize that topotecan will be most effective in patients whose tumors exhibit high pretreatment levels of topoisomerase I. It is also hypothesized that topotecan treatment will result in a diminution of topoisomerase I levels and an elevation of topoisomerase II levels above baseline. The objectives are to 1) determine the response rate and duration of response, 2) observe the toxicity associated with this regimen, 3) to observe the effect in tumor biopsy samples, 4) to determine topotecan pharmacokinetic parameters and to correlate serum levels with toxicity and response to treatment and 5) to observe whether the activity of topoisomerase I and/or the extent of in vitro inhibition of topoisomerase I activity by topotecan in primary and metastatic non-small cell lung cancer correlate with clinical response to treatment with a topotecan-containing chemotherapy regimen.

该方案采用剂量密集化疗治疗方案 其利用了以下抑制剂之间的协同活性： 拓扑异构酶I和II。 这是一项I/II期临床试验， 晚期非小细胞肺癌患者，既往未接受过 化疗 我们假设，拓扑替康将是最有效的， 肿瘤表现出高治疗前拓扑异构酶水平的患者 I. 还假设拓扑替康治疗将导致 拓扑异构酶I水平降低和拓扑异构酶升高 II水平高于基线。 目标是：1）确定 反应率和反应持续时间，2）观察毒性 与此方案相结合，3）观察肿瘤活检的效果 样品，4）以确定拓扑替康药代动力学参数， 将血清水平与毒性和对治疗的反应相关联，以及5） 观察拓扑异构酶I的活性和/或其表达的程度， 托泊替康对原发性肝癌和肝癌组织中拓扑异构酶I活性的体外抑制作用 转移性非小细胞肺癌与临床反应相关性 用含托泊替康的化疗方案治疗。