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GICS 2014：卡培他滨/替莫唑胺治疗抵抗性神经内分泌瘤效果更好

2014-02-24 PCMC dxy

卡培他滨/替莫唑胺神经内分泌瘤
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正在进行中的2期临床试验的中期结果显示，不同类型的晚期神经内分泌瘤患者中有95%在接受卡培他滨/替莫唑胺新联合治疗方案后表现出疾病进展稳定或肿瘤消退的趋势，而这些患者此前接受标准高剂量奥曲肽治疗后恶化。患者缓解时间长，中位无进展生存期为30个月，大部分患者仅出现一般程度的副作用。文章作者表示，卡培他滨/替莫唑胺二药联合治疗因其高出一筹的有效性，或可取代晚期神经内分泌瘤的所有其他二线治疗方案。1月1

正在进行中的2期临床试验的中期结果显示，不同类型的晚期神经内分泌瘤患者中有95%在接受卡培他滨/替莫唑胺新联合治疗方案后表现出疾病进展稳定或肿瘤消退的趋势，而这些患者此前接受标准高剂量奥曲肽治疗后恶化。患者缓解时间长，中位无进展生存期为30个月，大部分患者仅出现一般程度的副作用。

文章作者表示，卡培他滨/替莫唑胺二药联合治疗因其高出一筹的有效性，或可取代晚期神经内分泌瘤的所有其他二线治疗方案。1月16日至18日在圣弗朗西斯科举行的2014年胃肠癌研讨会（Gastrointestinal Cancers Symposium）上报告了上述研究结果。

纽约Presbyterian医院副教授、本研究的首席作者Robert Fine博士表示，在本研究中，我们发现一些预期寿命仅有6个月的患者在开始卡培他滨/替莫唑胺治疗8年后仍然存活。一些肿瘤患者经其他标准治疗如化疗、高剂量奥曲肽治疗，小分子抑制剂治疗、放疗、手术治疗等未出现缓解，而卡培他滨/替莫唑胺联合治疗对上述患者人群可能有效。此外，联合治疗与严重副作用发生率低相关，无住院或治疗相关性死亡。

研究细节

作为研究的一部分，共有28例不同转移性神经内分泌瘤亚型患者在试验中得到治疗。所有患者肿瘤分化良好或一般，这是典型的神经内分泌瘤。所有受试患者的疾病经标准治疗如高剂量奥曲肽治疗后出现进展，或基于奥曲肽扫描阴性结果而不适于上述治疗。

神经内分泌瘤生长缓慢，故经常对化疗产生抵抗。在神经内分泌瘤细胞的实验室研究中，研究者发现氟尿嘧啶(5-FU)可使替莫唑胺的抗肿瘤活性增加3倍。在本研究中，研究者精心设计了药物剂量和给药顺序（先卡培他滨后替莫唑胺）以使联合治疗方案的疗效达到最大。Fine医生称，先口服5-FU化疗可减少胸苷积累，进而改善替莫唑胺抗肿瘤效应2至4倍。

结局

几乎所有的患者均可从卡培他滨和替莫唑胺联合治疗中获得临床益处，并且这一联合疗法可使43%的患者获利肿瘤消退，使54%的患者肿瘤增长趋于稳定。两种非常难治的神经内分泌瘤亚型—良性肿瘤和脑垂体肿瘤患者中均可观察到高缓解率。12例良性瘤患者中有41%出现肿瘤消退；鉴于上述患者对化疗的典型缓解率仅为0%到4%，上述结果显得非常惊人。

研究者发现，在4例对放疗、化疗及手术治疗抵抗的脑垂体瘤患者中，经卡培他滨/替莫唑胺联合治疗后有2例出现完全缓解，1例肿瘤大小缩小了75%，还有1例在5年的时间里病情稳定。

最近的一次数据分析显示，中位无进展生存期接受30个月，有25%的患者超过4年。中位总生存期超过25个月。研究者正致力于使卡培他滨/替莫唑胺联合治疗更加有效，如与血小板衍生生长因子通路阻滞因子相结合。研究者称上述疗法有望用于脑肿瘤和黑色素瘤，对于这两种肿瘤，替莫唑胺是一种重要的治疗选择。

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    2014-04-14 gwc392

    #分泌#

    0

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    2014-03-09 lily1616

    #神经内分泌#

    0

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    2014-11-26 yige2012

    #抗性#

    0

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    2014-03-02 122.227.241.57

    舒尼替尼方案？

    0

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    2014-02-26 w363522449

    #卡培他滨#

    0

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    2014-02-26 weiz

    #神经内分泌瘤#

    0