Baidu
map

EASL 2014:LY2157299治疗晚期HCC的安全性剂量评估

2014-04-14 佚名 dxy

TGF-β信号转导与肝细胞癌(HCC)进展为中低分化肿瘤的过程有关,而抑制该信号转导通路可改善HCC患者整体生存率;LY2157299(LY)是一种TGF-β受体激酶抑制剂,可应用LY对HCC患者进行治疗。意大利巴里大学医学院传染病免疫内科Giannelli等对此进行了一项II期临床试验,旨在评估该药的安全剂量、疗效和药动学情况。 研究纳入对象为索拉非尼(SF)治疗后病情恶化者,或不能接受SF治疗

TGF-β信号转导与肝细胞癌(HCC)进展为中低分化肿瘤的过程有关,而抑制该信号转导通路可改善HCC患者整体生存率;LY2157299(LY)是一种TGF-β受体激酶抑制剂,可应用LY对HCC患者进行治疗。意大利巴里大学医学院传染病免疫内科Giannelli等对此进行了一项II期临床试验,旨在评估该药的安全剂量、疗效和药动学情况。

研究纳入对象为索拉非尼(SF)治疗后病情恶化者,或不能接受SF治疗的晚期HCC患者。研究对象Child-Pugh分级为HCC A/B7,AFP≥1.5×ULN,ECOG评分≤1,可测量病灶(RECIST 1.1)。

对患者间断给予LY 14天,28天一周期。将患者分为两个LY给药剂量组,分别为A组 160mg/d、B组 300mg/d。主要观察终点为病情发生进展的时间(TTP)和每种剂量给药下生物标志物的变化情况;次要观察终点包括毒性(CTCAE,V 4.0)、药代动力学和总生存期。

结果显示,109例入组患者(A组 37人;B组72人)的基线特征A组/B组分别为:中位年龄61岁/63岁;PS=0.60%/53%;病因为HCV感染30%/38%、HBV感染27%/24%、酒精性24%/25%;之前接受过SF治疗78%/83%;AFP≥200ng/ml 59%/63%。

总体中位TTP为12周,A组为12.1周、B组为10.0周。初次接受SF治疗者TTP为18.3周。有24%患者出现AFP下降超过20%。最常见的3/4级相关不良反应为:中性粒细胞减少(N = 3)、贫血(N = 3)、疲劳(N = 1)。

按比例进行剂量暴露,LY剂量160mg/d和300mg/d的AUC0-∞分别为3.8mg·h/L和7.0mg·h/L,不同HCC患者间暴露量有轻度差异。

研究表明,300mg/d的LY给药剂量具有可控范围内的毒性和抗肿瘤活性,该剂量可用于今后HCC治疗参考给药的相关研究。

版权声明:
本网站所有内容来源注明为“梅斯医学”或“MedSci原创”的文字、图片和音视频资料,版权均属于梅斯医学所有。非经授权,任何媒体、网站或个人不得转载,授权转载时须注明来源为“梅斯医学”。其它来源的文章系转载文章,或“梅斯号”自媒体发布的文章,仅系出于传递更多信息之目的,本站仅负责审核内容合规,其内容不代表本站立场,本站不负责内容的准确性和版权。如果存在侵权、或不希望被转载的媒体或个人可与我们联系,我们将立即进行删除处理。
在此留言
评论区 (4)
#插入话题
  1. [GetPortalCommentsPageByObjectIdResponse(id=1703995, encodeId=a1a41e0399566, content=<a href='/topic/show?id=286a59e974d' target=_blank style='color:#2F92EE;'>#晚期HCC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=59797, encryptionId=286a59e974d, topicName=晚期HCC)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0aab30610862, createdName=caobinglei8089, createdTime=Sat Jun 28 01:39:00 CST 2014, time=2014-06-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1259474, encodeId=69bf12594e437, content=<a href='/topic/show?id=2200854517' target=_blank style='color:#2F92EE;'>#HCC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8545, encryptionId=2200854517, topicName=HCC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=智智灵药, createdTime=Wed Apr 16 04:39:00 CST 2014, time=2014-04-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1412506, encodeId=3ce714125069d, content=<a href='/topic/show?id=ebcd6442dc' target=_blank style='color:#2F92EE;'>#EASL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6442, encryptionId=ebcd6442dc, topicName=EASL)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a0c52872504, createdName=kord1983, createdTime=Wed Apr 16 04:39:00 CST 2014, time=2014-04-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1519168, encodeId=33bc15191688d, content=<a href='/topic/show?id=2082286e7b' target=_blank style='color:#2F92EE;'>#ASL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2867, encryptionId=2082286e7b, topicName=ASL)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c1a311248160, createdName=lq1771, createdTime=Wed Apr 16 04:39:00 CST 2014, time=2014-04-16, status=1, ipAttribution=)]
  2. [GetPortalCommentsPageByObjectIdResponse(id=1703995, encodeId=a1a41e0399566, content=<a href='/topic/show?id=286a59e974d' target=_blank style='color:#2F92EE;'>#晚期HCC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=59797, encryptionId=286a59e974d, topicName=晚期HCC)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0aab30610862, createdName=caobinglei8089, createdTime=Sat Jun 28 01:39:00 CST 2014, time=2014-06-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1259474, encodeId=69bf12594e437, content=<a href='/topic/show?id=2200854517' target=_blank style='color:#2F92EE;'>#HCC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8545, encryptionId=2200854517, topicName=HCC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=智智灵药, createdTime=Wed Apr 16 04:39:00 CST 2014, time=2014-04-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1412506, encodeId=3ce714125069d, content=<a href='/topic/show?id=ebcd6442dc' target=_blank style='color:#2F92EE;'>#EASL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6442, encryptionId=ebcd6442dc, topicName=EASL)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a0c52872504, createdName=kord1983, createdTime=Wed Apr 16 04:39:00 CST 2014, time=2014-04-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1519168, encodeId=33bc15191688d, content=<a href='/topic/show?id=2082286e7b' target=_blank style='color:#2F92EE;'>#ASL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2867, encryptionId=2082286e7b, topicName=ASL)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c1a311248160, createdName=lq1771, createdTime=Wed Apr 16 04:39:00 CST 2014, time=2014-04-16, status=1, ipAttribution=)]
    2014-04-16 智智灵药
  3. [GetPortalCommentsPageByObjectIdResponse(id=1703995, encodeId=a1a41e0399566, content=<a href='/topic/show?id=286a59e974d' target=_blank style='color:#2F92EE;'>#晚期HCC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=59797, encryptionId=286a59e974d, topicName=晚期HCC)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0aab30610862, createdName=caobinglei8089, createdTime=Sat Jun 28 01:39:00 CST 2014, time=2014-06-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1259474, encodeId=69bf12594e437, content=<a href='/topic/show?id=2200854517' target=_blank style='color:#2F92EE;'>#HCC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8545, encryptionId=2200854517, topicName=HCC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=智智灵药, createdTime=Wed Apr 16 04:39:00 CST 2014, time=2014-04-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1412506, encodeId=3ce714125069d, content=<a href='/topic/show?id=ebcd6442dc' target=_blank style='color:#2F92EE;'>#EASL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6442, encryptionId=ebcd6442dc, topicName=EASL)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a0c52872504, createdName=kord1983, createdTime=Wed Apr 16 04:39:00 CST 2014, time=2014-04-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1519168, encodeId=33bc15191688d, content=<a href='/topic/show?id=2082286e7b' target=_blank style='color:#2F92EE;'>#ASL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2867, encryptionId=2082286e7b, topicName=ASL)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c1a311248160, createdName=lq1771, createdTime=Wed Apr 16 04:39:00 CST 2014, time=2014-04-16, status=1, ipAttribution=)]
    2014-04-16 kord1983
  4. [GetPortalCommentsPageByObjectIdResponse(id=1703995, encodeId=a1a41e0399566, content=<a href='/topic/show?id=286a59e974d' target=_blank style='color:#2F92EE;'>#晚期HCC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=59797, encryptionId=286a59e974d, topicName=晚期HCC)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0aab30610862, createdName=caobinglei8089, createdTime=Sat Jun 28 01:39:00 CST 2014, time=2014-06-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1259474, encodeId=69bf12594e437, content=<a href='/topic/show?id=2200854517' target=_blank style='color:#2F92EE;'>#HCC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8545, encryptionId=2200854517, topicName=HCC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=智智灵药, createdTime=Wed Apr 16 04:39:00 CST 2014, time=2014-04-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1412506, encodeId=3ce714125069d, content=<a href='/topic/show?id=ebcd6442dc' target=_blank style='color:#2F92EE;'>#EASL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6442, encryptionId=ebcd6442dc, topicName=EASL)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a0c52872504, createdName=kord1983, createdTime=Wed Apr 16 04:39:00 CST 2014, time=2014-04-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1519168, encodeId=33bc15191688d, content=<a href='/topic/show?id=2082286e7b' target=_blank style='color:#2F92EE;'>#ASL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2867, encryptionId=2082286e7b, topicName=ASL)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c1a311248160, createdName=lq1771, createdTime=Wed Apr 16 04:39:00 CST 2014, time=2014-04-16, status=1, ipAttribution=)]
    2014-04-16 lq1771

相关资讯

JCO:曹广文等发现核苷/核苷类似物可改善乙肝病毒相关肝细胞癌患者术后生存

研究要点: 1.旨在研究核苷/核苷类似物治疗对乙肝病毒相关肝细胞癌患者预后的影响。 2.两阶段纵向研究,第一阶段针对非随机干预队列评估NA治疗对接受手术治疗乙肝病毒相关肝细胞癌患者预后情况的影响;第二阶段为随机临床试验,旨在验证第一阶段结果。 3.核苷/核苷类似物治疗可有效恢复患者肝脏功能,降低HBV-HCC复发率并改善术后患者生存。 4.邻近部位肝组织的Ct-HBx表达水平可作为抗病毒治

JCO:台湾大学郑安理教授发现舒尼替尼治疗肝细胞癌结局不优于索拉非尼

研究要点: 本临床III期试验对比考察了舒尼替尼与索拉非尼治疗肝细胞癌的效果。 研究结果表明,舒尼替尼OS显著劣于索拉菲尼;舒尼替尼与较多且较严重的不良事件(AE)有关。 亚洲及乙肝感染患者的OS结局相当;接受索拉非尼治疗的丙肝患者可取得较好的OS结局。 在2013年9月30日在线出版的《临床肿瘤学杂志》(Journal of Clinical Oncology)上,发表了中国台湾大学郑安

Ann Surg:广西医科大学钟鉴宏等发现肝脏切除治疗BCLC B/C期肝细胞癌可取得较佳生存获益

研究要点: 目前在肝脏切除治疗BCLC B/C期HCC方面存在争议,本研究对肝脏切除与TACE的疗效与安全性进行了考察; 肝脏切除可取得优于TACE的生存获益;孤立性大型肿瘤、多结节肿瘤、大血管侵犯或PHT均非HR的禁忌症; 甲胎蛋白水平大于或等于400 ng/mL、糖尿病、大血管侵犯及PHT为BCLC B/C期HCC患者不良预后的独立预测因素。 尽管欧洲肝病研究协会与美国肝病研究协会

JID:1b期研究发现ITX5061治疗HCV效果有限

慢性HCV感染可引起肝硬化和肝细胞癌,是肝相关疾病发病和死亡的主要原因。现有的HCV治疗并不尽如人意,存在毒性、效果局限和顺应性差等缺点。尽管在细节方面仍存在诸多不清之处,但是HCV进入细胞所需要的细胞受体包括清道夫受体B类1型(SR-B1)、CD81、紧密连接蛋白1和闭锁蛋白。存在于多种细胞(包括肝细胞)膜上的整合跨膜蛋白ITX5061是一个高效的小分子SR-B1抑制剂。因为抑制SR-B1与血浆

EASL 2014:BCLC-B亚分类或对HCC患者预后有一定价值

2012年最新公布的巴塞罗纳临床肝癌分期系统(BarcelonaClinic Liver Cancer Classification,BCLC)-B亚分类标准,将存在中间阶段异质性的肝细胞癌(HCC)人群,按Child-Pugh评分、肿瘤负荷(最大到七个标准)、ECOG –PS和门静脉血栓形成,进一步划分为4个亚组。然而,该分类法尚未得到外部广泛地验证。 奥地利维也纳医科大学消化内科Hucke等对

Gastroenterology:关新元教授发现OSGIN1与肝癌进展有关

来自香港大学、新加坡国立大学和中山大学的研究人员证实,氧化应激诱导生长抑制因子1(OSGIN1)等位基因失衡与肝癌的进展相关。这一研究发现于1月10日发表在国际胃肠病学杂志(,IF 11.675)上。 任职于香港大学和中山大学肿瘤防治中心的关新元(Xin-Yuan Guan)教授是这篇论文的通讯作者。其主要研究领域包括肿瘤发生发展相关基因、肿瘤干细胞及肿瘤微环境等。在

Baidu
map
Baidu
map
Baidu
map