TOPOTECAN & ETOPOSIDE IN ADVANCED NON SMALL CELL LUNG CANCER

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， 既往化疗。 我们假设拓扑替康将是最 在肿瘤表现出高治疗前水平的 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， 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 3）观察其对肿瘤细胞的作用 活检样本，4）至 测定拓扑替康药代动力学参数 并将血清水平与毒性和对治疗的反应相关联 5）观察拓扑异构酶I活性和/或 拓扑替康对拓扑异构酶I活性的体外抑制程度 在原发性和转移性非小细胞肺癌中 对含托泊替康化疗治疗的临床反应 方案. 19例患者入组，仅1例部分 缓解，1例疾病稳定，13例疾病进展，4例 不可评价。根据对患者的审查，该试验已关闭 符合所提供的"提前停止规则"的反应数据 在方案的统计部分。

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.