Dose-response effect of eribulin in preclinical models of osteosarcoma by the pediatric preclinical testing consortium.

Dose-response effect of eribulin in preclinical models of osteosarcoma by the pediatric preclinical testing consortium.
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儿科临床前测试联盟在骨肉瘤临床前模型中艾日布林的剂量反应效应。

DOI:
10.1002/pbc.28606
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发表时间:
2020-10
影响因子:
3.2
通讯作者:
Gorlick R
Gorlick R
中科院分区:
医学3区
文献类型:
--
作者:
Gill J;Zhang W;Zhang Z;Roth M;Harrison DJ;Rowshan S;Erickson S;Gatto G;Kurmasheva R;Houghton P;Teicher B;Smith MA;Kolb EA;Gorlick R

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儿科临床前试验项目先前证明了艾日布林在骨肉瘤患者来源的异种移植物(PDX)模型中的活性。在复发性骨肉瘤患者中进行的II期试验未能达到缓解终点。在原始和扩展的PDX模型组中评估艾日布林,并在多个剂量水平和时间表下测试以评估剂量反应。在最高剂量下观察到最大反应,与既往结果一致。另一种时间表也产生了类似的反应。我们在骨肉瘤PDX模型中证明了艾日布林的陡峭剂量反应,这意味着任何偏离有效浓度的偏差都可能对活性产生显著影响。
The pediatric preclinical testing program previously demonstrated activity of eribulin in osteosarcoma patient-derived xenograft (PDX) models. The phase 2 trial in patients with relapsed osteosarcoma failed to meet response endpoints. Eribulin was evaluated in the original and an expanded set of PDX models and tested at multiple dose levels and schedules to evaluate dose-response. Maximal response was observed at the highest dose, consistent with prior results. The alternative schedule generated similar responses. We demonstrate steep dose-response for eribulin in osteosarcoma PDX models, implying that any deviation from achievement of effective concentrations may have a significant impact on activity.
DOI: 10.1158/0008-5472.can-04-1169
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