International Journal of Medical Sciences

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23 October 2017

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Int J Med Sci 2010; 7(1):48-54. doi:10.7150/ijms.7.48

Research Paper

Effect of dose-escalation of 5-fluorouracil on circadian variability of its pharmacokinetics in Japanese patients with Stage III/IVa esophageal squamous cell carcinoma

Akiko Kuwahara1, Motohiro Yamamori2, Kohshi Nishiguchi 3,4, Tatsuya Okuno 3, Naoko Chayahara 3, Ikuya Miki 3, Takao Tamura 3, Kaori Kadoyama2, Tsubasa Inokuma 2, Yoshiji Takemoto 2, Tsutomu Nakamura3, Kazusaburo Kataoka 1, Toshiyuki Sakaeda 2,3

1. School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya 663-8179, Japan
2. Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan
3. Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
4. Faculty of Pharmaceutical Sciences, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan

Abstract

Objective: 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.

Methods: 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/m2/day (the standard dose group, N=27) or 500-550 mg/m2/day (the high dose group, N=8) for days 1-5 and 8-12, infusion of cisplatin at 40 mg/m2/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 conclusions: 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.

Keywords: esophageal squamous cell carcinoma, 5-fluorouracil, plasma concentration, circadian rhythm, dose-escalation

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How to cite this article:
Kuwahara A, Yamamori M, Nishiguchi K, Okuno T, Chayahara N, Miki I, Tamura T, Kadoyama K, Inokuma T, Takemoto Y, Nakamura T, Kataoka K, Sakaeda T. Effect of dose-escalation of 5-fluorouracil on circadian variability of its pharmacokinetics in Japanese patients with Stage III/IVa esophageal squamous cell carcinoma. Int J Med Sci 2010; 7(1):48-54. doi:10.7150/ijms.7.48. Available from http://www.medsci.org/v07p0048.htm