Sequential oral 9-nitrocamptothecin and etoposide: a pharmacodynamic- and pharmacokinetic-based phase I trial.
Sequential oral 9-nitrocamptothecin and etoposide: a pharmacodynamic- and pharmacokinetic-based phase I trial.
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序贯口服 9-硝基喜树碱和依托泊苷：一项基于药效学和药代动力学的 I 期试验。
DOI：
10.1158/1535-7163.mct-06-0034
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发表时间：
2006
影响因子：
5.7
通讯作者：
Munster,PamelaN
中科院分区：
文献类型：
--
作者：
Simon,GeorgeR;Lush,RichardM;Gump,Jana;Tetteh,Leticia;Williams,Charles;Cantor,Alan;Antonia,Scott;Garrett,Christopher;Rocha-Lima,Caio;Fishman,Mayer;Sullivan,DanielM;Munster,PamelaN
Purpose:Resistance to topoisomerase (topo) I inhibitors has been related to down-regulation of nuclear target enzyme, whereas sensitization to topo II inhibitors may result from induction of topo II by topo I inhibitors. Here, we evaluated a sequence-specific administration of a topo I inhibitor followed by a topo II inhibitor.Experimental Design:Twenty-five patients with advanced or metastatic malignancies were treated with increasing doses (0.75, 1.0, 1.25, 1.5, 1.75, or 2.0 mg/m2) of 9-nitrocamptothecin (9-NC) on days 1 to 3, followed by etoposide (100 or 150 mg/d) on days 4 and 5. At the maximally tolerated dose, 20 additional patients were enrolled. The median age was 60 years (range, 40–84 years). Endpoints included pharmacokinetic analyses of 9-NC and etoposide, and treatment-induced modulations of topo I and II expression in peripheral blood mononuclear cells.Results:Neutropenia, thrombocytopenia, nausea, vomiting, diarrhea, and fatigue were dose-limiting toxicities and occurred in six patients. Despite a median number of four prior regimens (range 1–12), 2 (4%) patients had an objective response and 13 (29%) patients had stable disease. In contrast to the expected modulation in topo I and IIα levels, we observed a decrease in topo IIα levels, whereas topo I levels were not significantly altered by 9-NC treatment.Conclusions:Sequence-specific administration of 9-NC and etoposide is tolerable and active. However, peripheral blood mononuclear cells may not be a predictive biological surrogate for drug-induced modulation of topo levels in tumor tissues and should be further explored in larger studies. [Mol Cancer Ther 2006;5(8):2130–7]
1,25-二羟基维生素 D 的细胞受体测定及其在临床研究中的应用。
影响因子：
5.8
作者：
S. Manolagas;F. Culler;J. Howard;A. Brickman;L. Deftos
通讯作者：
L. Deftos
来自 cDNA 克隆的大鼠肠道维生素 D 依赖性钙结合蛋白序列。
影响因子：
4.8
作者：
C. Desplan;O. Heidmann;J. Lillie;C. Auffray;M. Thomasset
通讯作者：
M. Thomasset
钙转运蛋白、钙吸收和维生素 D。
影响因子：
18.2
作者：
Wasserman,RH;Fullmer,CS
通讯作者：
Fullmer,CS