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

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 Okuno³, Naoko Chayahara³, Ikuya Miki³, Takao Tamura³, Kaori Kadoyama², Tsubasa Inokuma², Yoshiji Takemoto², Tsutomu Nakamura³, Kazusaburo Kataoka¹, 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

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

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. Available from http://www.medsci.org/v07p0048.htm