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Crit Rev Oncol Hematol:转移性/进展期胃癌患者疾病进展后,是否行三线全身治疗?

2017-07-31 佚名 肿瘤资讯

晚期胃癌一线、二线治疗进展后是选择支持治疗还是继续三线治疗,三线治疗的获益与毒副作用是否可以平衡,目前均无明确定论。香港的Chan教授在Crit Rev Oncol Hematol杂志上发表了其系统综述研究,结果表明三线治疗有一定程度生存获益。

晚期胃癌一线、二线治疗进展后是选择支持治疗还是继续三线治疗,三线治疗的获益与毒副作用是否可以平衡,目前均无明确定论。香港的Chan教授在Crit Rev Oncol Hematol杂志上发表了其系统综述研究,结果表明三线治疗有一定程度生存获益。

研究背景

胃癌是第五大常见癌症,第三大癌症死亡病因,虽然治疗不断改善,但复发率仍达40–80%,一半患者诊断时已为进展期不适合手术。过去10年来,一线/二线化疗±靶向治疗已成为进展期/转移性胃癌的标准治疗,Cochrane综述和meta分析证实一线化疗较最佳支持治疗(BSC)有生存获益,中位生存分别为11和4.3个月,且联合化疗优于单药治疗。研究进一步证实病情进展后的二线治疗同BSC相比仍能进一步改善生存,减少死亡风险18%。

部分患者在二线治疗进展后一般状态依旧良好。研究显示,20–90%的此类患者将继续进行≥三线的治疗,以控制病情、改善症状、维持生活质量(QOL)和改善生存。紫杉类药物和依立替康是三线治疗中最常用的选择,总反应率10–25%,无进展生存(PFS)2.1–3.3个月,总生存(OS)5.6–10.9个月,韩国的一项III期RCT研究证实三线单药依立替康或多西他赛化疗趋向于生存更优,最近有关Her-2/EGFR/VEGFR/cMET/ATM/FGFR/IGFR/mTOR/PD-L1靶向治疗的研究正在进行中,疗效需要进一步探讨。

本项研究的意义在于,胃癌≥三线的治疗数据结论并不一致,缺少≥三线治疗的国际标准,因此该篇综述拟评估三线治疗的有效性和毒性反应,以供临床应用参考。

研究结果

共纳入6项研究,890例患者,三线治疗(TLT)587例,BSC303例,研究表明中位OS利于全身治疗组,TLT与BSC分别为4.80和3.20个月,PFS也是TLT组更优,不过结果的解释必需谨慎,因为存在异质性,包括地域、种族、原发部位和应用化疗药物与靶向药物的不同。

研究中纳入的患者只能部分代表所有胃癌患者,纳入研究中的患者通常更年轻,一般状态良好,患有未控制的高血压、静脉血栓、肝肾功能减低的患者通常不会纳入研究,因此不清楚那些老年、一般状态差、具有合并症的患者是否也可从化疗获益;而且这项研究中纳入的患者75%以上均为亚裔,非亚裔患者采用TLT治疗的有效性和耐受性仍需进一步评估。因此这项研究的结果不足以广泛外推适合所有二线治疗失败的胃癌患者。

研究显示,三线治疗产生获益的药物均为靶向药物,这些药物使用方便,无需住院。通常认为靶向药物的副作用更少,耐受性更优,也就是说骨髓抑制、恶心呕吐等副反应在靶向药物治疗时发生频率更低。不过靶向药物也有其较为独特的副反应,如高血压、蛋白尿和手足综合征,致死性并发症包括肺炎和胃肠道出血,这些副反应在三线治疗中均可见到。

既往的治疗可能也会影响TLT的有效性,因此应将化疗药物,包括氟脲嘧啶、铂剂和紫杉类药物以及靶向药物,如曲妥珠单抗和雷莫芦单抗进行整合,统一安排,以保证治疗的连续性和完整性,有助于患者在TLT时耐受性更优、获益更多。

当患者一般状态好、并发症少、预期生命≥3个月、愿意承受不良反应时应考虑使用TLT,治疗前医师应充分评估患者的预期与TLT并不突出的获益,以及相应的毒副反应是否能够达到平衡,需要医患双方的充分沟通,并告知除了TLT,还有BSC可供治疗选择。

随着对胃癌发生机制的探讨,有望开发更多靶向治疗药物,目前在研的靶向药物及其作用的信号途径包括HGF/c-MET途径、PI3K/AKT/mTOR途径、免疫节点等,抗HGF单抗Rilotumumab、抗c-MET单抗onartuzumab、瑞格非尼、帕姆单抗等都在进行临床研究,瑞格非尼和抗PD1/PDL1药物的有效性已初见端倪,也许在不久的将来,细胞毒化疗与靶向治疗、免疫治疗的联合会给进展期胃癌患者带来更多的生存获益和生活质量的改善。

此外这项研究中发现有关QOL的数据非常少,未来研究中应注意评估TLT与BSC时QOL的差别,同时还要评估QOL的相关结果。

研究不足

纳入研究均有商业赞助,易发生报告偏倚;数据采用的是累积数据,而非个体患者数据;BSC治疗并非标准化;需要进一步评估TLT与BSC的花费效益。

总之这项研究提示,TLT治疗有一定程度获益,不过需要付出毒副反应的代价,在开始TLT前需与患者充分沟通。二线治疗后的QOL数据缺乏,未来研究重点是不同药物的最优联合与排序,以保证治疗获益最大化和毒副反应最小化。

评论

胃癌是预后较差的肿瘤之一,复发转移/局部进展期肿瘤治疗手段匮乏,一线和二线治疗进展后,是继续三线治疗还是转入BSC治疗的相关数据并不充分,这项研究比较谨慎的给出了对三线治疗的肯定态度。同时,也强调其生存延长的代价是毒副反应的增加,因此需要对现有治疗药物的整合以保证获益最大化,也需要开发新的毒副作用更小、疗效更显着的药物。

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    2018-07-12 minlingfeng
  4. 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    2017-08-02 随梦飞扬

    最佳支持治疗(BSC)

    0

  5. 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  6. 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    2017-08-02 cscdliu

    学习了,非常感谢

    0

  7. 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    2017-08-02 fengyi812
  8. 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  9. 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    2017-08-01 三生有幸9135

    学习一下谢谢分享

    0

  10. [GetPortalCommentsPageByObjectIdResponse(id=1769643, encodeId=e6c91e69643e4, content=<a href='/topic/show?id=900b8323461' target=_blank style='color:#2F92EE;'>#胃癌患者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83234, encryptionId=900b8323461, topicName=胃癌患者)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=377c38086944, createdName=huhuaidong400, createdTime=Thu Oct 12 09:52:00 CST 2017, time=2017-10-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1907675, encodeId=680e190e67592, content=<a href='/topic/show?id=fdcee0731d2' target=_blank style='color:#2F92EE;'>#疾病进展#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=70731, encryptionId=fdcee0731d2, topicName=疾病进展)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5662228, createdName=mjldent, createdTime=Mon Mar 12 10:52:00 CST 2018, time=2018-03-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1865052, encodeId=3b441865052e3, content=<a href='/topic/show?id=16ce133504e' target=_blank style='color:#2F92EE;'>#Oncol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13350, encryptionId=16ce133504e, topicName=Oncol)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b63894, createdName=minlingfeng, createdTime=Thu Jul 12 05:52:00 CST 2018, time=2018-07-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=229254, encodeId=faa722925482, content=最佳支持治疗(BSC), beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/08/02/7354b3539aae6a0ccb1e0fff04c12084.jpg, createdBy=205b1984786, createdName=随梦飞扬, createdTime=Wed Aug 02 18:45:16 CST 2017, time=2017-08-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1814030, encodeId=028d181403092, content=<a href='/topic/show?id=edff943e88a' target=_blank style='color:#2F92EE;'>#进展期#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=94378, encryptionId=edff943e88a, topicName=进展期)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5fca128, createdName=licz0423, createdTime=Mon May 14 22:52:00 CST 2018, time=2018-05-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=229212, encodeId=699122921242, content=学习了,非常感谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/10/23/557c1f19aaf5459a8405411e38903c4b.jpg, createdBy=dfc02088287, createdName=cscdliu, createdTime=Wed Aug 02 15:50:30 CST 2017, time=2017-08-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1317342, encodeId=4e96131e34281, content=<a href='/topic/show?id=74916e0414' target=_blank style='color:#2F92EE;'>#EMA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6704, encryptionId=74916e0414, topicName=EMA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a35a460, createdName=fengyi812, createdTime=Wed Aug 02 11:52:00 CST 2017, time=2017-08-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1386260, encodeId=24b01386260be, content=<a href='/topic/show?id=f08293399f9' target=_blank style='color:#2F92EE;'>#转移性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93399, encryptionId=f08293399f9, topicName=转移性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1ac22500003, createdName=1249842em09(暂无昵称), createdTime=Wed Aug 02 11:52:00 CST 2017, time=2017-08-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=228868, encodeId=57a02288688c, content=学习一下谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzaiabIFicf63hKvVMjL6aJlx4yX4UcXmzX9DyibCRcicq0QtCRWMaQKh8MYjE1D3EKUBopgiaGWYuqbeR/0, createdBy=0c2b1999806, createdName=三生有幸9135, createdTime=Tue Aug 01 15:28:33 CST 2017, time=2017-08-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=228830, encodeId=3a7f228830fa, content=谢谢分享,学习了谢谢分享,学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4o2XVpJ6449yqDsjibydI5HnJ8MibGxNn4HZiaZib0bdfibbwoz3KQrIyN9AGxq36ZlZRNicYlPfOOWMtwgsajY6mGNFiaPclFdowjD0/0, createdBy=97bd1338592, createdName=清风拂面, createdTime=Tue Aug 01 12:40:52 CST 2017, time=2017-08-01, status=1, ipAttribution=)]
    2017-08-01 清风拂面

    谢谢分享,学习了谢谢分享,学习了

    0

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