对照组总缓解率高,有统计学意义。余晓忠[6]及周梅娟等[7]也进行类似疗效观察,都得出培美曲塞/顺铂是治疗晚期食管癌有效方案的结论。同时 Li BS等[8]Ⅰ期临床研究显示培美曲塞/顺铂同步放疗治疗局部晚期食管鳞癌,入组12例患者,CR 8例,PR 4例,反应率为100%。国内试验结果令人鼓舞,培美曲塞治疗食管癌安全有效。培美曲塞无食管癌治疗指征,机制方面研究尚无报道。有研究显示食管癌治疗前胸苷酸合成酶(TS)表达高与5-Fu为基础的化疗无反应有关[9]。另有观察者利用RT-PCR分析25种食管鳞癌细胞系后,发现TS过表达的细胞系对5-Fu越耐药[10]。TS是5-Fu靶酶之一,其高表达可能预测食管癌对5-Fu等化疗药的敏感性,而TS同样也是培美曲塞的重要靶酶之一,其高低能否决定培美曲塞对食管癌的疗效尚需进一步研究。许多研究证实TS高表达可能与多种肿瘤对培美曲塞耐药有关,其中TS高表达与NSCLC对培美曲塞不敏感有关[11-12]。因此,笔者推测食管癌对培美曲塞化疗敏感可能与两患者肿瘤组织TS表达低有关。
本研究分析两例患者均为晚期食管鳞癌,一线应用多西他赛加铂类化疗进展换用培美曲塞后转移淋巴结均消失,一般状况好转,疗效显著。目前有报道显示吉西他滨治疗复治性食管癌TTP 4.8月[13],两例晚期食管鳞癌二线培美曲塞治疗后TTP均超过目前研究结果,显示出良好的抗瘤性。因此,我们认为应用培美曲塞治疗晚期食管癌有较好的前景,但仍需进行大样本随机对照研究,以进一步证实。
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