Inoue Yasuhiro, Miki Chikao, Watanabe Hideki, Hiro Junichiro, Toiyama Yuji, Ojima Eiki, Nakatani Kaname, Nobori Tsutomu, Kusunoki Masato
Division of Reparative Medicine, Department of Gastrointestinal and Pediatric Surgery, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie 514-8507, Japan.
Oncol Rep. 2006 Nov;16(5):971-4.
We have previously demonstrated that the combined use of doxifluridine and irinotecan shows a different molecular mechanism than that of the protracted venous infusion of 5-FU and irinotecan. In this analysis, there is a suggestion that doxifluridine may enhance irinotecan and enable us to decrease the dose of irinotecan without losing the strong effect by using doxifluridine instead of 5-FU. We present a colon cancer patient with the UGT1A1 polymorphism (UGT1A1 *28) as a known high risk for irinotecan, who was treated with a combination of doxifluridine and irinotecan for peritoneal dissemination resulting in stable disease for 2 years without adverse reactions, although the patient initially developed severe adverse effects to the combination of the protracted venous infusion of 5-FU and irinotecan. Even with the same ratios of fluoropyrimidine and irinotecan combinations, replacing 5-FU with doxifluridine or capecitabine could provide new strategies to obtain not only convenience but also better efficacy and safety at the molecular level.
我们之前已经证明，多西氟尿苷与伊立替康联合使用显示出与5-氟尿嘧啶持续静脉输注和伊立替康联合使用不同的分子机制。在该分析中，有迹象表明多西氟尿苷可能增强伊立替康的作用，并且使我们能够在不损失强效效果的情况下，通过使用多西氟尿苷而非5-氟尿嘧啶来降低伊立替康的剂量。我们报告了一名患有UGT1A1基因多态性（UGT1A1 *28）的结肠癌患者，已知该基因多态性是伊立替康的高风险因素，该患者接受了多西氟尿苷与伊立替康联合治疗腹膜播散，疾病稳定2年且无不良反应，尽管该患者最初对5-氟尿嘧啶持续静脉输注和伊立替康联合治疗出现了严重不良反应。即使氟嘧啶与伊立替康联合使用的比例相同，用多西氟尿苷或卡培他滨替代5-氟尿嘧啶不仅可以提供便利，还能在分子水平上获得更好的疗效和安全性。
