Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2010 Jan 31;7(1):48-54.
doi: 10.7150/ijms.7.48.

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 Kuwahara  1 , Motohiro Yamamori, Kohshi Nishiguchi, Tatsuya Okuno, Naoko Chayahara, Ikuya Miki, Takao Tamura, Kaori Kadoyama, Tsubasa Inokuma, Yoshiji Takemoto, Tsutomu Nakamura, Kazusaburo Kataoka, Toshiyuki Sakaeda
Affiliations
Clinical Trial

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 Kuwahara et al. Int J Med Sci. .

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/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 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: 5-fluorouracil; circadian rhythm; dose-escalation; esophageal squamous cell carcinoma; plasma concentration.

PubMed Disclaimer

Conflict of interest statement

Competing Interest: The authors declare that no conflict of interest exists.

Figures

Figure 1
Figure 1
Protocol of a definitive 5fluorouracil (5-FU)/ cisplatin (CDDP)-based chemoradiotherapy. One course of treatment consisted of protracted venous infusions of 5-FU (400 or 500-550 mg/m2/day for days 1-5 and 8-12) and CDDP (40 mg/m2/day on days 1 and 8), and radiation (2 Gy/day on days 1-5, 8-12, and 15-19), with a second course (days 36-56) repeated after a 2-week interval.
Figure 2
Figure 2
Circadian variation of plasma concentrations of 5fluorouracil (5-FU) in patients with advanced esophageal cancer. A total of 8 measurements were made per patient: 5:00 PM on days 3, 10, 38 and 45, and 5:00 AM on days 4, 11, 39 and 46. Closed circle: the standard dose group (N=27), open circle: the high dose group (N=8). The bars represent the SD. * P < 0.05 in the standard dose group, ** P < 0.05 in the high dose group.
See this image and copyright information in PMC

References

    1. Cooper JS, Guo MD, Herskovic A. et al. Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). Radiation Therapy Oncology Group. JAMA. 1999;281:1623–7. - PubMed
    1. Herskovic A, Martz K, Al-Sarraf M. et al. Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N Eng J Med. 1992;326:1593–8. - PubMed
    1. Begg C, Cho M, Eastwood S. et al. Improving the quality of reporting of randomized controlled trials. The CONSORT statement. JAMA. 1996;276:637–9. - PubMed
    1. Al-Sarraf M, Martz K, Herskovic A. et al. Progress report of combined chemoradiotherapy versus radiotherapy alone in patients with esophageal cancer: an intergroup study. J Clin Oncol. 1997;15:277–84. - PubMed
    1. Ohtsu A, Boku N, Muro K. et al. Definitive chemoradiotherapy for T4 and/or M1 lymph node squamous cell carcinoma of the esophagus. J Clin Oncol. 1999;17:2915–21. - PubMed

Publication types

MeSH terms