理论水平的临床试验bexarotene在非小细胞肺癌患者。

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Dragnev KH、小WJ沙SJ,刘易斯LD,黑色CC, Memoli V,纽金特WC,赫尔曼·T Negro-Vilar,里加斯小,Dmitrovsky E

理论水平的临床试验bexarotene在非小细胞肺癌患者。

癌症研究杂志2007年3月15日,13 (6):1794 - 800。

PubMed ID

17363535 (在PubMed

]

文摘

目的:Bexarotene rexinoid(选择性视黄素X受体激动剂),影响细胞增殖,分化,细胞凋亡在临床前研究。bexarotene水平和生物标志物之间的关系没有以前研究肿瘤组织的变化。实验设计:BEAS-2B人类支气管上皮细胞(HBE), retinoid-resistant BEAS-2B-R1细胞,A427 H226, H358肺癌细胞bexarotene对待。核扩散和生物标志物表达进行评估。在理论水平的临床试验,bexarotene肿瘤组织水平和瘤内药效学影响患者的评估阶段II非小细胞肺癌。Bexarotene(300毫克/米(2)/天)是管理范围为7 - 9天前切除。结果:Bexarotene-induced是剂量依赖性抑制增长,细胞周期蛋白D1,细胞周期素D3,总表皮生长因子受体(EGFR),在BEAS-2B phospho-EGFR表达式,BEAS-2B-R1, A427, H358,但不是H226细胞。12个病人登记,和10可评价的。Bexarotene治疗耐受良好。有非线性等离子体和肿瘤bexarotene浓度之间的相关性(r (2) = 0.77)。 Biomarker changes in tumors were observed: repression of cyclin D1, total EGFR and proliferation in one case; repression of cyclin D3, total and phospho-EGFR in another. The cases with multiple biomarker changes had high tumor bexarotene (107-159 ng/g). A single biomarker change was detected in one case with low tumor bexarotene. CONCLUSION: Bexarotene represses proliferation and biomarker expression in responsive, but not resistant HBE and lung cancer cells. Similar biomarker changes occur in lung tumors when therapeutic intratumoral bexarotene levels are achieved. This proof-of-principle trial approach is useful to uncover pharmacodynamic mechanisms in vivo and relate these to intratumoral pharmacokinetic effects.

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药物

Bexarotene