The impact of bevacizumab on temozolomide concentrations in intracranial U87 gliomas.
The impact of bevacizumab on temozolomide concentrations in intracranial U87 gliomas.
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DOI：
10.1007/s00280-012-1867-1
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发表时间：
2012-07
影响因子：
3
通讯作者：
Blakeley, Jaishri O.
中科院分区：
文献类型：
--
作者：
Grossman, Rachel;Rudek, Michelle A.;Brastianos, Harry;Zadnik, Patti;Brem, Henry;Tyler, Betty;Blakeley, Jaishri O.
在胶质母细胞瘤(GBM)患者的抗癌治疗顺序中，一个重要的问题是同时进行的抗血管生成治疗是改善还是损害同时给予的细胞毒治疗的脑浓度。本研究的目的是评估替莫唑胺(TMZ)在贝伐单抗治疗前后通过微透析在颅内GBM异种移植模型中的瘤内处理情况。在荷U87脑胶质瘤的裸鼠的肿瘤内和对侧脑内放置微透析探针。10天后给予TMZ(50 mg/kg)灌胃。收集细胞外液(ECF)6h，静脉注射Bev(10 mg/kg)，36h后再次给予TMZ(50 mg/kg)，并收集ECF。用液相色谱-串联质谱法对所有ECF样品进行TMZ浓度评估。剂量-时间曲线下的肿瘤平均面积(AUC0-∞)为3.35μg h/mLBev前。BEV后，肿瘤平均TMZAUC0-∞为3.98μg h/mL。在非肿瘤脑组织中，BEV前TMZ AUC0-∞平均值为3.22μg h/mL，BEV后TMZ AUC0-BEV平均值为3.34μg h/mL。在裸鼠U87脑胶质瘤模型中，BEV前后TMZ的药代动力学无统计学意义的变化。在几项正在进行的胶质瘤患者研究中，BEV和TMZ正在作为一种联合疗法进行研究。这些数据令人放心地表明，在TMZ之前36小时给药，BEV并没有显著改变TMZ在荷瘤或正常脑组织中的ECF浓度。
An important question in the sequencing of anti-cancer therapies in patients with glioblastoma (GBM) is whether concurrent anti-angiogenesis therapies improve or impair brain concentrations of concomitantly administered cytotoxic therapies. The purpose of this study is to assess the intratumoral disposition of temozolomide (TMZ) via microdialysis before and after bevacizumab in an intracranial GBM xenograft model. Microdialysis probes were placed within tumor and contralateral brain in athymic rats bearing U87 intra-cerebral gliomas. TMZ (50 mg/kg oral) was administered 10 days thereafter. Extracellular fluid (ECF) was collected for 6 h. BEV was administered (10 mg/kg IV), and TMZ was re-dosed (50 mg/kg oral) 36 h thereafter with additional ECF collection. All ECF samples were assessed for TMZ concentration with liquid chromatography–tandem mass spectrometry. Tumor TMZ mean area under the concentration–time curve (AUC0–∞) was 3.35 μg h/mL pre-BEV. Post-BEV, tumor mean TMZ AUC0–∞ was 3.98 μg h/mL. In non-tumor brain, mean TMZ AUC0–∞ pre-BEV was 3.22 μg h/mL and post-BEV was 3.34 μg h/mL. There were no statistically significant changes in TMZ pharmacokinetics before or after BEV in the athymic rat U87 intracranial glioma model. BEV and TMZ are being investigated as a combination therapy in several ongoing studies for patients with glioma. These data reassuringly suggest that BEV does not significantly change the ECF tumor concentrations of TMZ in either tumor-bearing or normal brain when dosed 36 h prior to TMZ.
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影响因子：
11.5
作者：
Kim, KJ;Wang, LH;Laterra, J
通讯作者：
Laterra, J
影响因子：
4.1
作者：
McGirt MJ;Than KD;Weingart JD;Chaichana KL;Attenello FJ;Olivi A;Laterra J;Kleinberg LR;Grossman SA;Brem H;Quiñones-Hinojosa A
通讯作者：
Quiñones-Hinojosa A
影响因子：
4.8
作者：
Mathieu, Veronique;De Neve, Nancy;Lefranc, Florence
通讯作者：
Lefranc, Florence
DOI：
10.1158/1078-0432.ccr-09-3106
发表时间：
2010-04-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Grossman SA;Ye X;Piantadosi S;Desideri S;Nabors LB;Rosenfeld M;Fisher J;NABTT CNS Consortium
通讯作者：
NABTT CNS Consortium
影响因子：
3
作者：
Jacobs S;McCully CL;Murphy RF;Bacher J;Balis FM;Fox E
通讯作者：
Fox E