CLIN CANCER RES:BRAF和HSP90抑制剂联合治疗不可切除的黑色素瘤

2018-11-20 MedSci MedSci原创

BRAF抑制剂对晚期BRAF V600突变黑色素瘤患者具有临床活性,但获得性耐药仍然很常见。临床前研究表明,使用HSP90抑制剂XL888联合治疗可以克服耐药性。CLIN CANCER RES近期发表了一篇文章,报道了两种药物联合的临床试验结果

BRAF抑制剂对晚期BRAF V600突变黑色素瘤患者具有临床活性,但获得性耐药仍然很常见。临床前研究表明,使用HSP90抑制剂XL888联合治疗可以克服耐药性。CLIN CANCER RES近期发表了一篇文章,报道了两种药物联合的临床试验结果。

研究纳入21例晚期BRAF V600 -mutant黑素瘤患者。患者接受Vemurafenib(960毫克p.o.bid)联合递增剂量的XL888(30,45,90,或135毫克口服每周两次)治疗。主要研究终点是安全性和确定最大耐受剂量。通过蛋白质组学研究确认HSP抑制剂活性。研究结果表明,在20名可评估的患者中有15名观察到客观缓解,包括3名完全缓解和12名部分缓解。中位无进展生存期和总生存期分别为9.2个月和34.6个月。最常见的3/4级毒性是皮肤毒性,如皮疹(n = 4,19%)和皮肤鳞状细胞癌(n = 3,14%),以及腹泻(n= 3,14%)。在XL888剂量≥45mg的三个队列中,患者外周血单核细胞(PBMC)的药效学分析显示,与基线相比,第8天HSP70表达增加。

文章最后认为,XL888联合Vemurafenib治疗晚期BRAF V600 -mutant黑色素瘤患者具有临床活性,副作用可耐受。HSP90抑制剂与当前标准的BRAF加MEK抑制剂相联合治疗BRAF V600 -mutant黑素瘤患者需进一步研究。

原始出处:

Zeynep Eroglu, Y. Ann Chen, et al. Combined BRAF and HSP90 Inhibition in Patients with Unresectable BRAFV600E-Mutant Melanoma. CLIN CANCER RES. November 2018 doi: 10.1158/1078-0432.CCR-18-0565

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    2019-05-12 jklm09
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    2019-05-29 sunylz
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    2018-11-22 zhaojie88
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