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

• Published in: International journal of medical sciences Vol. 7; no. 1; pp. 48 - 54
• Main Authors: Kuwahara, Akiko, Yamamori, Motohiro, Nishiguchi, Kohshi, Okuno, Tatsuya, Chayahara, Naoko, Miki, Ikuya, Tamura, Takao, Kadoyama, Kaori, Inokuma, Tsubasa, Takemoto, Yoshiji, Nakamura, Tsutomu, Kataoka, Kazusaburo, Sakaeda, Toshiyuki
• Format: Journal Article
• Language: English
• Published: Australia Ivyspring International Publisher 31.01.2010
• Subjects: Aged; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - blood; Antineoplastic Combined Chemotherapy Protocols - pharmacokinetics; Asian Continental Ancestry Group; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Circadian Rhythm - drug effects; Circadian Rhythm - physiology; Cisplatin - administration & dosage; Cisplatin - adverse effects; Dose-Response Relationship, Drug; Esophageal Neoplasms - drug therapy; Esophageal Neoplasms - metabolism; Esophageal Neoplasms - pathology; Female; Fluorouracil - administration & dosage; Fluorouracil - adverse effects; Fluorouracil - blood; Fluorouracil - pharmacokinetics; Humans; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Staging; Research Paper; Treatment Outcome; 5-fluorouracil; esophageal squamous cell carcinoma; dose-escalation; plasma concentration; circadian rhythm
• ISSN: 1449-1907; 1449-1907
• 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.