Randomized phase II study of two schedules of topotecan in previously treated patients with ovarian cancer: A National Cancer Institute of Canada Clinical Trials Group Study
Randomized phase II study of two schedules of topotecan in previously treated patients with ovarian cancer: A National Cancer Institute of Canada Clinical Trials Group Study
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DOI：
10.1200/jco.1998.16.6.2233
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发表时间：
1998-06-01
影响因子：
45.3
通讯作者：
Zee, B
中科院分区：
文献类型：
--
作者：
Hoskins, P;Eisenhauer, E;Zee, B
目的：由于托泊替康是 S 期特异性的，因此其功效可能依赖于时间表。因此，我们进行了一项采用“挑选获胜者”设计的随机研究，以比较复发性卵巢癌患者的两种治疗方案。 患者和方法：之前接受过不超过两种单独化疗方案（其中一种必须是含铂）的复发性上皮性卵巢癌患者被随机分配至托泊替康 1.5 mg/m(2) 静脉注射 (IV)，每天超过 30 分钟，持续 5 天，每 21 天重复一次（A 组，标准组），或托泊替康1.75 mg/m(2) 24 小时输注，每周一次，持续 4 周，每 6 周重复一次（B 组，实验组）。结果：66 名患者符合条件，63 名患者可评估反应。 A 组的缓解率为 22.6%（95% 置信区间 [CI]，9.6% 至 41.2%），显着优于 B 组的 3.1%（95% CI，0.1% 至 16%）（P=0.026）。治疗方案的毒性并不相同，A 组中有 94% 的患者出现 3 级或 4 级粒细胞减少症，而 B 组的这一比例为 52%。 B 组结论：每周 24 小时输注拓扑替康 1.75 mg/m(2) 对复发性卵巢癌无效。每天五次的时间表仍然是首选的时间表。由于这些方案的毒性并不相同，因此无法区分无效的方案和无效的剂量，从而作为反应率不同的原因。然而，已经发生的骨髓毒性程度将排除每周治疗方案中任何显着更高的剂量。 (C) 1998 年美国临床肿瘤学会。
Purpose: As topotecan is S-phase-specific, its efficacy is likely schedule-dependent. Therefore, a randomized study using a "pick the winner" design was undertaken to compare two schedules in patients with recurrent ovarian cancer.Patients and Methods: Patients with recurrent epithelial ovarian cancer previously treated with no more than two separate regimens of chemotherapy, one of which had to be platinum-containing, were randomized to either topotecan 1.5 mg/m(2) intravenously (IV) over 30 minutes daily for 5 days repeated every 21 days (arm A, the standard arm), or topotecan 1.75 mg/m(2) as a 24-hour infusion once a week for 4 weeks repeated every 6 weeks (arm B, the experimental arm).Results: Sixty-six patients were eligible and 63 were assessable for response. The response rate in arm A was 22.6% (95% confidence interval [CI], 9.6% to 41.2%), which was significantly superior to that in arm B, 3.1% (95% CI, 0.1% to 16%) (P=.026), The regimens were not equitoxic, with 94% of patients on arm A experiencing grade 3 or 4 granulocytopenia as opposed to 52% on arm B.Conclusion: The weekly 24 hour infusion of topotecan at 1.75 mg/m(2) was ineffective in relapsed ovarian cancer. The daily-times-five schedule remains the schedule of choice. As the regimens were not equitoxic, one cannot differentiate between an ineffective schedule and an ineffective dose as the reason for the differing response rates. However, the degree of myelotoxicity that already occurs will preclude any substantially higher dosing with the weekly regimen. (C) 1998 by American Society of Clinical Oncology.