• Akiko Kuwahara, Motohiro Yamamori, Kohshi Nishiguchi, Tatsuya Okuno, Naoko Chayahara, Ikuya Miki, Takao Tamura, Kaori Kadoyama, Tsubasa Inokuma, Yoshiji Takemoto, Tsutomu Nakamura, Kazusaburo Kataoka, and Toshiyuki Sakaeda.
• School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya 663-8179, Japan.
• Int J Med Sci. 2010 Jan 31; 7 (1): 485448-54.

ObjectiveThe 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.MethodsThirty-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.Results And ConclusionsNo 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.

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