Optimal biologic dose of metronomic chemotherapy regimens is associated with maximum antiangiogenic activity
Optimal biologic dose of metronomic chemotherapy regimens is associated with maximum antiangiogenic activity
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DOI：
10.1182/blood-2005-04-1422
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发表时间：
2005-11-01
期刊：
影响因子：
20.3
通讯作者：
Kerbel, RS
中科院分区：
文献类型：
--
作者：
Shaked, Y;Emmenegger, U;Kerbel, RS
低剂量节律化疗被认为具有抗血管生成的基础，是一种有前途的治疗性癌症的策略。然而，降低毒性、在某些情况下提高功效以及将以这种方式长期施用的联合收割机化疗与靶向治疗相结合的能力的优点可能会受到与确定最佳生物剂量（OBD）相关的药物敏感性的损害。在4种不同的临床前肿瘤模型（包括血液恶性肿瘤）中使用4种不同的节拍化疗方案，我们通过确定与最小或无毒性相关的最大疗效来建立OBD。然后，我们发现每个OBD与活的外周血循环血管内皮生长因子受体2阳性（VEGFR-2（+））内皮前体（CEP）的最大减少显著相关。这些结果表明，CEP可以作为一个药效学生物标志物，以确定节拍化疗方案的OBD。
Low-dose metronomic chemotherapy is a promising therapeutic cancer treatment strategy thought to have an antiangiogenic basis. However, the advantages of reduced toxicity, increased efficacy in some cases, and ability to combine chemotherapy administered long term in this way with targeted therapies can be compromised by the empiricism associated with determining the optimum biologic dose (OBD). Using 4 distinct metronomic chemotherapy regimens in 4 different preclinical tumor models, including a hematologic malignancy, we established the OBD by determining the maximum efficacy associated With minimum or no toxicity. We then found each OBD to be strikingly correlated with the maximum reduction in viable peripheral blood circulating vascular endothelial growth factor receptor 2-positive (VEGFR-2(+)) endothelial precursors (CEPs). These results suggest that CEPs may serve as a pharmacodynamic biomarker to determine the OBD of metronomic chemotherapy regimens.