标准治疗选择:

多项临床研究验证了标准化疗和最佳支持疗法在治疗转移性胃癌中的效果,目前的共识认为接受化疗的患者平均生存时间较接受支持疗法的患者可延长数月[11][12][13]。[ 证据等级:1iiA]过去的二十年中,多项随机临床研究评估了不同治疗方案(单药化疗与联合化疗)对治疗方案尚存争议的转移性胃癌患者的效果。一项荟萃分析显示,联合化疗相较于单一疗法具有相对优势,总生存率(OS)的危险比(HR)为0.83(95%可信区间[CI]:0.74-0.93)[14]

所有联合化疗方案中,ECF方案常被美国和欧洲国家作为参考标准。欧洲一项临床研究将274例转移性食管-胃癌患者随机分组接受ECF或FAMTX化疗[15]。ECF组的中位生存时间明显长于FAMTX组(分别为8.9与5.7个月,P=0.0009)[15]。[ 证据等级:1iiA]另一项研究比较了ECF方案与MCF方案(丝裂霉素、顺铂联合5-FU),两组患者的生存时间无统计学显著差异(分别为9.4与8.7个月,P=0.315)[5]。[ 证据等级:1iiA​]

根据REAL-2临床研究( ISRCTN51678883)的结果[6],奥沙利铂与卡培他滨目前常用于替换ECF方案中的顺铂与5-FU[6]。该随机研究共有1002例患有晚期食管、胃食管交界处或胃癌患者入组,研究使用2×2分组方案,显示卡培他滨治疗的患者中位总生存率不劣于5-FU治疗的患者(死亡率HR=0.86,95%CI:0.82-0.99),亦不劣于奥沙利铂取代顺铂治疗的患者(死亡率HR=0.92,95%CI:0.80-1.10)。

一项国际协作临床研究中445例转移性胃癌患者被随机分组接受多西他赛、顺铂联合5-FU的DCF化疗方案或者是CF方案治疗[16]。选择疾病进展时间(TTP)为主要终点。DCF组的患者TTP显著延长(DCF组5.6个月,95%CI:4.9-5.9;CF组3.7个月,95%CI:3.4-4.5;HR:1.47;95%CI:1.9-1.82;时序检验 P<0.001;风险减少32%)。DCF组患者的总生存时间(OS)中位数明显长于CF组(DCF组9.2个月,95%CI:8.4-10.6;CF组8.6个月,95%CI:7.2-9.5;HR:1.29,95%CI:1.0-1.6;时序检验 P=0.02;风险减少23%)[16]。[ 证据等级:1iiA]两组均观察到高毒性反应发生率[17]。DCF方案组更多观察到致热性中性粒细胞减少(分别为29%和12%),DCF方案组患者死亡率为10.4%,而CF方案组则为9.4%。

对于转移性胃癌的患者,CF方案是否可作为参考方案仍有待进一步研究[17]。一项研究中,245例转移性胃癌患者被随机分组,分别接受CF、FAMTX或ELF方案治疗,研究结果显示三组的反应率、无进展生存率或总生存率(OS)无显著性差异[7]。三组患者出现3-4级中性粒细胞减少的比例均为35%-43%,而CF组严重恶心、呕吐的发生率更高,达26%[7]。[ 证据等级:1iiDiv​]

在一项国际开放性III期临床研究中,HER-2阳性的转移性、局部晚期无法手术或复发性胃癌或胃食管交界处癌患者被随机分配至两组,分别使用添加或不添加抗HER2单克隆抗体曲妥珠单抗的化疗方案[18]。若患者IHC染色3+或FISH显示HER2比CEP17大于等于2,则认为此患者为HER2阳性。此研究共有3,665例患者入组,810例患者HER2阳性(22%), 594例符合入选标准接受随机分组。化疗药物包括顺铂联合5-FU亦或卡培他滨,由研究者选择。患者每3周接受1次化疗,共6周期,同时每3周进行曲妥珠单抗给药,直至疾病进展、产生无法耐受的毒性反应或患者撤回知情同意书。疾病进展后患者不可改用曲妥珠单抗。曲妥珠单抗组的总生存时间(OS)中位数为13.8个月(95%CI: 12-16),而单用化疗组为11.1个月(95%CI:10-13)(HR:0.74;95%CI:0.60-0.91;P =0.0046)[18]。[ 证据等级:1iiA​]两组的不良事件发生率无显著性差异,心脏毒性在两组中均罕见。

对于一线化疗后疾病进展的患者,尚无标准的治疗选择。韩国一项研究中,接受过1-2种化疗方案(含氟嘧啶与铂剂)的晚期胃癌患者以2:1比例被随机分配至两组,分别接受补救性化疗和最佳支持治疗[19]。补救性化疗由医生选择多西他赛(每3周60 mg/m2)或伊立替康(每2周150 mg/m2)中的一种。在参与研究的202例患者中,133例患者接受补救性化疗,69例患者接受最佳支持治疗。补救性化疗组总生存时间中位数为5.3个月,最佳支持治疗组则为3.8个月(HR:0.657;P=0.007)。使用多西他赛与伊立替康的患者中位总生存时间无显著差异(分别为5.2与6.5个月,P= .116)[19]。[ 证据等级:1iiA​]

​处于临床评估阶段的治疗选择:

下列药物应用于姑息性化疗伊立替康与顺铂叶酸,5-FU联合伊立替康(FOLFIRI)亚叶酸钙,5-FU联合奥沙利铂(FOLFOX)

​II期临床研究显示,使用基于伊立替康或奥沙利铂的化疗方案后,患者反应率与TTP与行ECF或CF方案治疗的患者相似,且前者毒性反应更少[20][21][22][23][24][25]。关于方案相对有效性优劣,目前证据存在争议,多项研究正在评估这些新化疗方案的有效性。

目前开展的临床试验

​美国目前正在招募 IV 期胃癌患者进行临床试验,请参见美国NCI癌症临床试验列表,可根据部位、药物、其他干预或标准进行进一步筛选。

NCI网站还提供关于各项临床试验的基本信息。

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