Phase I studies of nogitecan hydrochloride for Japanese
Phase I studies of nogitecan hydrochloride for Japanese
复制标题
日本盐酸诺吉替康 I 期研究
DOI：
10.1007/s101470200026
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发表时间：
2002
影响因子：
3.3
通讯作者：
H. Niitani
中科院分区：
文献类型：
--
作者：
K. Kobayashi;M. Hino;M. Fukuoka;K. Takeuchi;K. Furuse;S. Yoneda;K. Hasegawa;K. Noda;H. Kinoshita;I. Kimura;T. Taguchi;R. Kanamaru;N. Horikoshi;H. Niitani
AbstractBackground。SmithKline Beecham合成喜树碱类似物，并鉴定出nogitecan hydrochloride （topotecan）具有广谱抗肿瘤活性，且毒性低于喜树碱。由于临床前和国外临床数据显示盐酸诺吉替康具有5天重复给药计划的抗肿瘤作用，我们在日本开展了I期研究，以确定盐酸诺吉替康的最大耐受剂量（MTD）、药代动力学和抗肿瘤作用。
AbstractBackground. SmithKline Beecham synthesized camptothecin analogs and identified nogitecan hydrochloride (topotecan) with a broad spectrum of antitumor activity and less toxicity than camptothecin. Because preclinical and overseas clinical data indicated the antitumor effect of nogitecan hydrochloride with a 5-day repeat-dose schedule, we carried out phase I studies in Japan to determine the maximum tolerated dose (MTD), pharmacokinetics, and antitumor effect of nogitecan hydrochloride.
Methods. Phase I studies of nogitecan hydrochloride given by single and 5-day repeat dosing were carried out in patients with various solid tumors at 15 medical institutions in Japan. Pharmacokinetic evaluations were performed for both single and 5-day repeated dosing.
Results. The dose-limiting factor (DLF) was reversible leucopenia, and the maximum tolerated dose (MTD) was higher than 22.5 mg/m2 in the single-dose study. In the 5-day repeat-dose study, the DLF was also reversible leucopenia, and the MTD was estimated to be 1.5 mg/m2 per day. The plasma concentration of nogitecan hydrochloride increased with increasing dose, and the half-life after single dosing ranged from 3 to 5 h. There was no evidence of accumulation or delayed excretion during 5-day repeat dosing.
Conclusion. Based on these results and the finding that there were responders among patients treated at 1.5 mg/m2 per day by 5-day repeat dosing in overseas studies, 5-day repeat dosing of 1.2 mg/m2 per day, one dose level lower than the MTD, was selected for phase II studies in Japan.
DOI：
10.1016/s0021-9258(18)90729-5
发表时间：
1984-11
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
G. L. Chen;L. Yang;T. Rowe;B. Halligan;K. M. Tewey;L. Liu
通讯作者：
G. L. Chen;L. Yang;T. Rowe;B. Halligan;K. M. Tewey;L. Liu