Goto Akira, Itoh Miki, Wakasugi Hideki, Kanno Shinichi, Yabana Takashi, Mitsuhashi Kei, Adachi Takeya, Kondo Yoshihiro, Suzuki Takashi, Shinomura Yasuhisa
Dept. of Gastroenterology, Otaru Municipal Hospital, Japan.
Gan To Kagaku Ryoho. 2012 Oct;39(10):1563-6.
S-1 and capecitabine are orally administered fluoropyridines reported to be effective in the treatment of advanced gastric cancer(AGC). In fact, both S-1/CDDP and capecitabine/CDDP are considered to be the standard first-line treatments for AGC.However, no information concerning on the activity of capecitabine in S-1-pretreated patients with AGC has been reported. Here, we present a case of recurrent gastric cancer that showed a partial response resulting in 6 months of progres-sion-free survival, thanks to capecitabine/CDDP after the failure of multiple anticancer drugs such as S-1/CDDP. S -1 and capecitabine may exhibit cross-resistance because they both have the same final active metabolite: 5-fluorouracil(5-FU). Dihydropyrimidine dehydrogenase(DPD)is the rate-limiting enzyme in the degradation of 5-FU, and S-1 contains the inhibitor of DPD. Thus, S-1, but not capecitabine, is active against tumors with high DPD expression. On the other hand, capecitabine is activated to 5-FU by thymidine phosphorylase(TP)within the tumor tissue and is more effective against tumors with high TP expression. The present case suggests that S-1 and capecitabine do not always exhibit cross-resistance, and that capecitabine may be effective in S-1-pretreated patients with AGC.
S-1和卡培他滨是口服氟代吡啶类药物，据报道对晚期胃癌（AGC）治疗有效。事实上，S-1/顺铂和卡培他滨/顺铂均被视为AGC的标准一线治疗方案。然而，尚无关于卡培他滨对接受过S-1预处理的AGC患者疗效的报道。在此，我们报告1例复发性胃癌患者，在S-1/顺铂等多种抗癌药物治疗失败后，采用卡培他滨/顺铂治疗，获得部分缓解，无进展生存期达6个月。S-1和卡培他滨可能存在交叉耐药性，因为它们具有相同的最终活性代谢产物：5-氟尿嘧啶（5-FU）。二氢嘧啶脱氢酶（DPD）是5-FU降解的限速酶，S-1含有DPD抑制剂。因此，S-1对高表达DPD的肿瘤有活性，而卡培他滨则不然。另一方面，卡培他滨在肿瘤组织内被胸苷磷酸化酶（TP）激活为5-FU，对高表达TP的肿瘤更有效。本病例提示，S-1和卡培他滨并不总是表现出交叉耐药性，卡培他滨可能对接受过S-1预处理的AGC患者有效。
