TOPOTECAN & ETOPOSIDE IN ADVANCED NON SMALL CELL LUNG CANCER

拓扑替康

• 批准号: 6246449
• 负责人: NATHAN LEVITAN
• 金额: $ 1.98万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-01-06 至 1997-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6246449
• 关键词: DNA topoisomerases; biopsy; clinical research; clinical trial phase I; dosage; drug adverse effect; drug screening /evaluation; enzyme activity; etoposide; human subject; 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.

该方案使用剂量强化化疗方案，该方案 利用抑制剂之间的协同活性 拓扑异构酶I和II。这是针对患者的I/II期临床试验 未接受治疗的晚期非小细胞肺癌患者 化疗。我们假设拓扑替康在 肿瘤患者的治疗前拓扑异构酶I水平较高。 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II水平升高 高于基线的水平。目标是1)确定回应 应答率和持续时间，2)观察与以下相关的毒性 该方案，3)观察肿瘤活检标本的效果，4) 拓扑替康药代动力学参数测定及血药浓度相关性研究 毒性和治疗反应的水平以及5)观察 拓扑异构酶I的活性和/或体外抑制程度 拓扑替康对原发和转移性非肿瘤组织中拓扑异构酶I活性的影响 小细胞肺癌与临床疗效的相关性研究 一种含有拓扑替康的化疗方案。