等离子体浓度vemurafenib发达BRAFV600mut黑色素瘤患者:对肿瘤反应的影响和宽容。

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安倍Funck-Brentano E,阿尔瓦雷斯JC, Longvert C, E, Beauchet, Funck-Brentano C, Saiag P

等离子体浓度vemurafenib发达BRAFV600mut黑色素瘤患者:对肿瘤反应的影响和宽容。

安杂志。2015年7月,26 (7):1470 - 5。doi: 10.1093 / annonc / mdv189。Epub 2015年4月21日。

PubMed ID

25899783 (在PubMed

]

文摘

背景:Vemurafenib改善生存发达BRAFV600(傻瓜)黑色素瘤患者,但宽容往往是贫穷和抵抗频繁发生,没有预测因素。我们的目的是调查首次vemurafenib等离子体浓度之间的关系(PVC)和功效和宽容。不可切除的转移性的方法:等离子体样本BRAFV600(傻瓜)黑色素瘤患者vemurafenib单一疗法是在每个肿瘤前瞻性收集响应评价(RECIST 1.1)或不良事件发生时(CTCAE 4.0)。PVC与液体chromatography-tandem质谱测量。在此,我们报告在PVC稳定状态(> / = 14天后vemurafenib介绍或剂量修改)。样品收集后第一个黑色素瘤进展被排除在响应分析。所有样品都是在公差分析分析。我们最接近的样本收集每个不利影响或发病最高的PVC没有不利影响。比较方式(学生的t和Wilcoxon排名和测试)和频率(chi(2)测试)。逻辑回归分析确定进展的预测因子。 RESULTS: We included 105 plasma samples in 23 patients (10M/13F). Initial vemurafenib dose was 960 mg b.i.d., reduced by 25% (8 patients) or 50% (2 patients) for intolerance in 10 patients (44%). PVC displayed high inter-individual variability (13.0-109.8 microg/ml, median 54.0). Mean PVC was lower at time of first progression (38.8 +/- 19.7 microg/ml) than mean PVC found when tumour was stable or in partial or complete response (56.4 +/- 21.0 microg/ml, P = 0.013, 21 patients). Logistic regression revealed that having a low PVC (P = 0.01) or brain metastasis (P = 0.01) were both significantly and independently associated with tumour progression. High PVC was not statistically significantly associated with the occurrence of adverse effects. CONCLUSION: PVC at steady state is highly variable and low PVC was associated with tumour progression, suggesting a new path to melanoma resistance to vemurafenib.

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药物转运蛋白

药物	转运体	类	生物	药理作用	行动
Vemurafenib	磷酸腺苷盒式sub-family 2 G的成员	蛋白质	人类	未知的	底物 抑制剂	细节