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EUR J Cancer:BRAF / MEK抑制剂的使用会产生脱髓鞘性多发性神经根神经病变

2017-12-28 MedSci MedSci原创

BRAF / MEK抑制剂和免疫治疗剂已经被批准用于治疗转移性BRAF突变的黑色素瘤

BRAF / MEK抑制剂和免疫治疗剂已经被批准用于治疗转移性BRAF突变的黑色素瘤,其中50%为皮肤黑色素瘤。然而法国研究者报道了BRAF / MEK抑制剂在治疗黑色素瘤过程中,患者产生了亚急性炎性脱髓鞘性多发性神经根神经病变的病例。这位60岁女性黑色素瘤患者的病程长达10年,在脑部病灶手术切除后,开始使用BRAF / MEK抑制剂:Vemurafenib(每日1920毫克)和cobimetinib(每日60 毫克),然而在经历了三周治疗后,由于不良反应问题,医生决定降低BRAF / MEK抑制剂的剂量:Vemurafenib(每日960毫克)和cobimetinib(每日20 毫克),然而在治疗九周后,患者产生了严重的刺痛感和灼烧感,并从脚下迅速转移至腿部,而这种严重不良反应持续了五周,直到治疗停止后才稳定。

研究人员对该患者产生的这些不良反应进行了详细的生理生化分析,最终确定Vemurafenibcobimetinib的使用导致了亚急性炎性脱髓鞘性多发性神经根神经病变。而这种BRAF / MEK抑制剂所带来的神经生理毒性的机制尚不清楚。

 

原始出处:

Devic, Perrine, et al. "Demyelinating polyradiculoneuropathy under combined BRAF/MEK inhibitors." European journal of cancer 2017 78: 103. doi.org/10.1016/j.ejca.

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    2018-05-18 jml2009
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topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200816/e4675a86ea694f12b82202b320dc2654/12f6b900498349e994ce8f516a584d6a.jpg, createdBy=09431951290, createdName=大爰, createdTime=Sun Jan 07 12:27:19 CST 2018, time=2018-01-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1354983, encodeId=43e31354983ad, content=<a href='/topic/show?id=6de63659ed' target=_blank style='color:#2F92EE;'>#BRAF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3659, encryptionId=6de63659ed, topicName=BRAF)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Sat Dec 30 08:37:00 CST 2017, time=2017-12-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1491296, encodeId=69d014912968d, content=<a href='/topic/show?id=5316e4387aa' target=_blank style='color:#2F92EE;'>#神经病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=74387, encryptionId=5316e4387aa, topicName=神经病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=1ab48885684, createdName=axin012, createdTime=Sat Dec 30 08:37:00 CST 2017, time=2017-12-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1500369, encodeId=76ae15003699b, content=<a href='/topic/show?id=ecdfe438970' target=_blank style='color:#2F92EE;'>#神经病变#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=74389, encryptionId=ecdfe438970, topicName=神经病变)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0ea69427176, createdName=lingaifan, createdTime=Sat Dec 30 08:37:00 CST 2017, time=2017-12-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1512729, encodeId=2c541512e2929, content=<a href='/topic/show?id=c3e91152873' target=_blank style='color:#2F92EE;'>#MEK抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11528, encryptionId=c3e91152873, topicName=MEK抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=318b10497059, createdName=ms2186806800017884, createdTime=Sat Dec 30 08:37:00 CST 2017, time=2017-12-30, status=1, ipAttribution=)]
    2018-04-23 jklm09
  5. 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topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200816/e4675a86ea694f12b82202b320dc2654/12f6b900498349e994ce8f516a584d6a.jpg, createdBy=09431951290, createdName=大爰, createdTime=Sun Jan 07 12:27:19 CST 2018, time=2018-01-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1354983, encodeId=43e31354983ad, content=<a href='/topic/show?id=6de63659ed' target=_blank style='color:#2F92EE;'>#BRAF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3659, encryptionId=6de63659ed, topicName=BRAF)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Sat Dec 30 08:37:00 CST 2017, time=2017-12-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1491296, encodeId=69d014912968d, content=<a href='/topic/show?id=5316e4387aa' target=_blank style='color:#2F92EE;'>#神经病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=74387, encryptionId=5316e4387aa, topicName=神经病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=1ab48885684, createdName=axin012, createdTime=Sat Dec 30 08:37:00 CST 2017, time=2017-12-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1500369, encodeId=76ae15003699b, content=<a href='/topic/show?id=ecdfe438970' target=_blank style='color:#2F92EE;'>#神经病变#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=74389, encryptionId=ecdfe438970, topicName=神经病变)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0ea69427176, createdName=lingaifan, createdTime=Sat Dec 30 08:37:00 CST 2017, time=2017-12-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1512729, encodeId=2c541512e2929, content=<a href='/topic/show?id=c3e91152873' target=_blank style='color:#2F92EE;'>#MEK抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11528, encryptionId=c3e91152873, topicName=MEK抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=318b10497059, createdName=ms2186806800017884, createdTime=Sat Dec 30 08:37:00 CST 2017, time=2017-12-30, status=1, ipAttribution=)]
    2018-01-09 naiwu77
  6. 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target=_blank style='color:#2F92EE;'>#神经病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=74387, encryptionId=5316e4387aa, topicName=神经病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=1ab48885684, createdName=axin012, createdTime=Sat Dec 30 08:37:00 CST 2017, time=2017-12-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1500369, encodeId=76ae15003699b, content=<a href='/topic/show?id=ecdfe438970' target=_blank style='color:#2F92EE;'>#神经病变#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=74389, encryptionId=ecdfe438970, topicName=神经病变)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0ea69427176, createdName=lingaifan, createdTime=Sat Dec 30 08:37:00 CST 2017, time=2017-12-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1512729, encodeId=2c541512e2929, content=<a href='/topic/show?id=c3e91152873' target=_blank style='color:#2F92EE;'>#MEK抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11528, encryptionId=c3e91152873, topicName=MEK抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=318b10497059, createdName=ms2186806800017884, createdTime=Sat Dec 30 08:37:00 CST 2017, time=2017-12-30, status=1, ipAttribution=)]
    2018-01-07 大爰

    学习了谢谢分享!

    0

  7. 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    2017-12-30 zhaojie88
  8. 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    2017-12-30 axin012
  9. 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目前尚无研究针对原发肿瘤位置对不同BRAF,RAS和微卫星灶不稳定(MSI)状态的接受结肠癌切除并进行标准辅助化疗的患者预后的影响。JAMA Oncology近期发表了一篇文章,研究Ⅲ期结肠癌患者接受FOLFOX联合或不联合西妥昔单抗治疗后不同BRAF,RAS和MSI状态原发肿瘤位置的预后价值。

J NATL CANCER I:BRAFV600突变非黑色素肿瘤的共存基因改变可影响生存?

BRAF突变可发生于非黑色素肿瘤中,靶向BRAF的药物却一直未能获批治疗此类肿瘤,这主要源于BRAF抑制剂对BRAF突变非黑色素肿瘤原发或继发耐药,肿瘤中与BRAFV600突变共存的基因改变可能与耐药相关,因此美国Sen教授分析了BRAFV600突变肿瘤的共存基因改变以及改变对BRAFV600抑制剂耐药、肿瘤PFS和OS的影响,研究结果发表在JNCI。

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