School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya 663-8179, Japan.
Int J Med Sci. 2010 Jan 31;7(1):48-54. doi: 10.7150/ijms.7.48.
The effects of dose-escalation of 5-fluorouracil (5-FU) on the clinical outcome and pharmacokinetics of 5-FU were investigated in Japanese patients with Stage III/IVa esophageal squamous cell carcinoma.
Thirty-five patients with Stage III/IVa were enrolled, who were treated with a definitive 5-FU/cisplatin-based chemoradiotherapy. A course consisted of continuous infusion of 5-FU at 400 mg/m(2)/day (the standard dose group, N=27) or 500-550 mg/m(2)/day (the high dose group, N=8) for days 1-5 and 8-12, infusion of cisplatin at 40 mg/m(2)/day on days 1 and 8, and radiation at 2 Gy/day on days 1 to 5, 8 to 12, and 15 to 19, with a second course repeated after a 2-week interval. Plasma concentrations of 5-FU were determined by high performance liquid chromatography at 5:00 PM on days 3, 10, 38 and 45, and at 5:00 AM on days 4, 11, 39 and 46.
No patient with Stage IVa achieved a complete response in the standard dose group, whereas a complete response was observed at a rate of 50% in the high dose group, and this can be explained by a higher plasma concentration of 5-FU. The circadian rhythm in the concentrations found at the standard dose was not observed for a higher dose.
研究氟尿嘧啶（5-FU）剂量递增对 III/IVa 期食管鳞癌日本患者的临床疗效和药代动力学的影响。
35 例 III/IVa 期患者接受了根治性 5-FU/顺铂化疗。一个疗程包括连续输注 5-FU 400 mg/m²/天（标准剂量组，N=27）或 500-550 mg/m²/天（高剂量组，N=8），第 1-5 天和第 8-12 天，第 1 天和第 8 天输注顺铂 40 mg/m²，第 1-5 天、第 8-12 天和第 15-19 天每天接受 2 Gy 放疗，2 周后重复第二疗程。在第 3、10、38 和 45 天下午 5:00 以及第 4、11、39 和 46 天上午 5:00 通过高效液相色谱法测定 5-FU 血浆浓度。
标准剂量组的 IVa 期患者无一例完全缓解，而高剂量组的完全缓解率为 50%，这可以用更高的 5-FU 血浆浓度来解释。在更高剂量下，未观察到标准剂量时发现的浓度的昼夜节律。
