Conceptual changes in cancer chemotherapy: from an oral fluoropyrimidine prodrug, UFT, to a novel oral fluoropyrimidine prodrug, S-1, and low-dose FP therapy in Japan
Conceptual changes in cancer chemotherapy: from an oral fluoropyrimidine prodrug, UFT, to a novel oral fluoropyrimidine prodrug, S-1, and low-dose FP therapy in Japan
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DOI：
10.1023/a:1006476730671
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发表时间：
2000-11-01
影响因子：
3.4
通讯作者：
Taguchi, T
中科院分区：
文献类型：
--
作者：
Shirasaka, T;Yamamitsu, S;Taguchi, T
癌症化疗的传统观念认为，如果不引起不良反应，就不可能达到有效的效果。我们基于一个新的概念提供了具体的描述，使我们能够摆脱旧的概念。缓解腹泻、口腔炎、厌食和H&F综合征等不良反应，不仅可以提高患者的生活质量，而且可以在不降低患者依从性的情况下延长疗程。本文描述了一种基于自救概念的治疗模式，具有双重活性，即增强效果和减少不良反应。我们介绍了新型口服氟嘧啶抗癌药物S-1的理论和实践，该药物旨在增强抗癌活性，减少胃肠道毒性。在UFT中使用的DPD抑制剂(CDHP)比尿嘧啶更有效；以及定位于胃肠道的ORTC抑制剂(Oxo)。5-FU(CIV)联合小剂量顺铂(CDDP)作为5-FU的调节剂；5-FU(CVI)间歇(周一、周三、周五)联合小剂量顺铂(CDDP)连续给药的理论和实践，利用胃肠道粘膜细胞与肿瘤细胞或骨髓细胞与肿瘤细胞周期的差异。我们打算在未来将上述引起较少不良反应的治疗方法与温和对待癌症患者相结合，以努力进一步延长他们的预期寿命。
The conventional concept in cancer chemotherapy considers that no efficacy can be attained without provoking adverse reactions. We presented concrete descriptions based on a novel concept allowing us to emerge from the old one. Relief of adverse reactions, e.g., diarrhea, stomatitis, anorexia, and H&F syndrome, not only improves QOL of the patient but also allows prolongation of the treatment period without lowering patient compliance.We describe in this paper a therapeutic modality which is based on SRC (self-rescuing concept) featuring dual activity, i.e., effect-enhancing activity and adverse reaction-reducing activity.We present the theory and practice of S-1, a novel oral fluoropyrimidine anticancer agent designed to enhance anticancer activity and reduce gastrointestinal toxicity through the deliberate combination of the following components: an oral fluoropyrimidine agent tegafur; a DPD inhibitor (CDHP) which is more potent than uracil used in UFT; and an ORTC inhibitor (Oxo) which localizes in the gastrointestinal tract. Furthermore, we refer to combination therapy with 5-FU (CIV) and low-dose consecutive CDDP in which CDDP was used as a modulator of 5-FU and to the theory and practice of combination therapy with 5-FU (CVI) intermittent (Monday, Wednesday, and Friday) administration and low-dose CDDP consecutive administration in which a difference in cell cycle between gastrointestinal mucosal cell and tumor cell or between bone marrow cell and tumor cell was utilized. We intend in future to combine the abovementioned therapeutic modalities provoking less adverse reactions and being gentle to patients with cancer in an effort to further increase their life expectancy.