edotecarin期和药代动力学研究,小说拓扑异构酶抑制剂,管理在实体肿瘤患者每3周。
文章的细节
-
引用
复制到剪贴板 -
山田Y,田村T,山本N, shinmoyama教授T,建筑师Y,村上H, Kusaba H, Kamiya Y,萨卡人H, Tanigawara Y, McGovren JP, Natsumeda Y
edotecarin期和药代动力学研究,小说拓扑异构酶抑制剂,管理在实体肿瘤患者每3周。
癌症Chemother杂志。2006年8月,58 (2):173 - 82。Epub 2005年11月25日。
- PubMed ID
-
16308697 (在PubMed]
- 文摘
-
目的:Edotecarin (j - 107088)是一个强大的indolocarbazole我拓扑异构酶抑制剂在结构上不同于喜树碱。本研究旨在确定最大耐受剂量(MTD),推荐剂量为未来二期研究和安全性、药代动力学资料,初步抗肿瘤活性edotecarin在晚期实体肿瘤患者人口。实验设计:Edotecarin管理作为单剂量静脉输液/ 2 h每21天(从毒性为1周允许复苏,如果需要)在晚期实体肿瘤患者。剂量范围从8到15毫克/米(2)。药代动力学进行了评估期间和之后第一个政府。结果:24例共收到了61个周期的治疗。Dose-limiting毒性(感染、发热性中性粒细胞减少、便秘、肠梗阻和延长4级粒细胞减少)在3的5名可观察15毫克/ m(2)剂量,定义MTD。最常报道non-hematologic毒性厌食,恶心,不舒服,便秘。腹泻频繁和严重。嗜中性白血球减少症是最常见的血液毒性(3 - 4级在21/23患者循环1)。edotecarin的血浆浓度迅速上升2小时输液开始后,达到C (max)值103 + / -17 ng / ml的13毫克/米(2)剂量,并注入结束后急剧下降。 Plasma concentrations declined to approximately 1-2 ng/ml at 26 h post start of infusion, the last PK sampling time point. The mean apparent plasma half-life of the drug was 20 h, which should be considered a preliminary estimate until results from studies with a longer duration of plasma sampling are available. A mean of 1.4-3.6% of the dose was recovered as unchanged drug in the urine over 48 h. Unconfirmed tumor regression > or =50% was observed in 2 patients, 1 with metastatic gastric carcinoma and 1 with esophageal cancer. CONCLUSIONS: The MTD of edotecarin administered IV over 2 h every 21 days was 15 mg/m(2). The recommended dose for Phase II studies with a 3-week schedule (with 1 week permitted for recovery from toxicities, if needed) is 13 mg/m(2). The observed safety profile and preliminary evidence of antitumor activity warrant further investigation of this drug in solid tumors.
beplay体育安全吗DrugBank数据引用了这篇文章
- 药物