TOPOTECAN & ETOPOSIDE IN ADVANCED NON SMALL CELL LUNG CANCER

拓扑替康

• 批准号: 6115280
• 负责人: NATHAN LEVITAN
• 金额: $ 2.33万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 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/6115280
• 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. Nineteen patients were enrolled with only one partial response, one stable disease, 13 developed progressive disease, 4 were not evaluable. This trail was closed based upon review of patient response data in compliance with the "early stopping rule" as provided in the statistical section of the protocol.

该方案采用剂量强化化疗方案。 它利用了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 尚未接受治疗的晚期非小细胞肺癌患者 之前接受过化疗。我们假设Topotecan将是最 在肿瘤的治疗前水平较高的患者中有效 拓扑异构酶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II水平高于基线。目标是1) 确定响应率和响应持续时间，2)观察 与该方案相关的毒性，3)观察其对肿瘤的影响 活检标本，4)测定拓扑替康的药代动力学参数 并将血清水平与毒性和治疗反应相关联 5)观察拓扑异构酶I的活性和/或 拓扑替康对拓扑异构酶I活性的体外抑制程度 原发和转移性非小细胞肺癌与 含拓扑替康的化疗方案的临床疗效 养生法。19名患者入选，只有一个部分 缓解，1例病情稳定，13例病情进展，4例 不可评估的。根据对患者的复查，该试验被关闭 符合所提供的“提前停止规则”的响应数据 在议定书的统计部分。