Phase II study of triapinea® in patients with metastatic renal cell carcinoma:: A trial of the national cancer institute of canada clinical trials group (NCIC IND.161)
Phase II study of triapinea® in patients with metastatic renal cell carcinoma:: A trial of the national cancer institute of canada clinical trials group (NCIC IND.161)
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DOI：
10.1007/s10637-007-9044-9
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发表时间：
2007-10-01
影响因子：
3.4
通讯作者：
Eisenhauer, Elizabeth A.
中科院分区：
文献类型：
--
作者：
Knox, Jennifer J.;Hotte, Sebastien J.;Eisenhauer, Elizabeth A.
Trivalidine（（R））是一种新型的小分子核糖核苷酸还原酶抑制剂，在肾细胞癌（RCC）细胞系中显示出活性。评价具有新机制的新药仍然是不可治愈的RCC患者的兴趣。这是一项单臂、多中心的II期试验，在复发性RCC患者中，Trilidone的给药方案为96 mg/m2，每日2小时输注，每2周重复4次。对19名符合条件的患者进行了中位4个周期的Trivalent治疗。有一个反应（7%）。中位进展时间为3.6个月。常见的不良事件（AE）为1-2级，其中疲劳占74%，恶心占68%，呕吐占58%。但79%患者出现3/4级中性粒细胞减少，并出现缺氧、低血压、高铁血红蛋白血症等急性反应。由于AE导致的剂量减少/延迟很常见，只有47%的患者接受> 90%的计划剂量强度。研究在第1阶段结束时关闭，因为其不符合继续进行的最低疗效标准。不建议在晚期肾癌患者中进一步评估Trilidone的剂量和时间表。
Triapine((R)) is a novel small molecule ribonucleotide reductase inhibitor that showed activity in renal cell carcinoma (RCC) cell lines. Evaluating new agents with novel mechanisms remains of interest for patients with incurable RCC. This was a single-arm, multicentre phase II trial where Triapine was given at a schedule of 96 mg/m(2) 2-h infusion daily x 4 repeated every 2 weeks in patients with recurrent RCC. A median of four cycles of Triapine was administered to 19 eligible patients. One response was seen (7%.) Median time to progression was 3.6 months. Common adverse events (AEs) were grade 1-2, with fatigue in 74%, nausea in 68% and vomiting in 58%. However grade 3/4 neutropenia was seen in 79% and acute reactions of hypoxia, hypotension, methemoglobinemia were seen. Dose reductions/delays due to AEs were common with only 47% of patients receiving > 90% of planned dose intensity. The study closed, at the end of stage 1 as it did not meet the minimal efficacy criteria to proceed. Further evaluation of Triapine at this dose and schedule in patients with advanced kidney cancer is not recommended.