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Article

Association between circadian and chemotherapeutic cycle effects on plasma concentration of 5‑fluorouracil and the clinical outcome following definitive 5‑fluorouracil/cisplatin‑based chemoradiotherapy in patients with esophageal squamous cell carcinoma

  • Authors:
    • Akiko Kuwahara
    • Shinji Kobuchi
    • Takao Tamura
  • View Affiliations / Copyright

    Affiliations: School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Hyōgo 663‑8179, Japan, Department of Pharmacokinetics, Kyoto Pharmaceutical University, Kyoto 607‑8414, Japan, Department of Medical Oncology, Kindai University Nara Hospital, Ikoma, Nara 630‑0293, Japan
  • Pages: 668-675
    |
    Published online on: October 16, 2018
       https://doi.org/10.3892/ol.2018.9586
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Abstract

Therapeutic drug monitoring (TDM) of 5‑fluorouracil (5‑FU) is believed to be a clinical option for improving clinical responses. Evaluating the potential factors contributing to plasma 5‑FU concentration is important to develop TDM of 5‑FU. Our aim was to evaluate the association of the circadian and treatment cycle effects on plasma 5‑FU concentration with the clinical response. A post hoc population analysis was performed using the plasma concentration of 5‑FU and clinical response data, including prognosis from 49 patients with esophageal squamous cell carcinoma after treatment with definitive 5‑FU/cisplatin‑based chemoradiotherapy, consisting of prolonged infusion of 5‑FU at 400 mg/(m2·day) for 5 days. The circadian rhythm and treatment cycle were applied as covariates to the model equation. The plasma 5‑FU concentration in the evening was 1.3‑fold higher compared with the morning, and in the second cycle, it was 1.5‑fold increased compared with the first cycle, with relatively small inter‑individual variations (23.3 and 16.8%). Clinical efficacy depended on the plasma 5‑FU concentration, excluding the covariate effects (P=0.025), which correlated with age and height but not body surface area. Circadian variation did not contribute to the clinical response, and the increase in 5‑FU plasma concentration in the second cycle significantly correlated with leucocyte counts obtained before chemoradiotherapy. The higher plasma concentration of 5‑FU in the early phase of treatment may be the key determinant of clinical efficacy, whereas the variations in the plasma concentration of 5‑FU owing to the time of day and treatment cycle are small contributors.
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Copy and paste a formatted citation
Spandidos Publications style
Kuwahara A, Kobuchi S and Tamura T: Association between circadian and chemotherapeutic cycle effects on plasma concentration of 5‑fluorouracil and the clinical outcome following definitive 5‑fluorouracil/cisplatin‑based chemoradiotherapy in patients with esophageal squamous cell carcinoma. Oncol Lett 17: 668-675, 2019.
APA
Kuwahara, A., Kobuchi, S., & Tamura, T. (2019). Association between circadian and chemotherapeutic cycle effects on plasma concentration of 5‑fluorouracil and the clinical outcome following definitive 5‑fluorouracil/cisplatin‑based chemoradiotherapy in patients with esophageal squamous cell carcinoma. Oncology Letters, 17, 668-675. https://doi.org/10.3892/ol.2018.9586
MLA
Kuwahara, A., Kobuchi, S., Tamura, T."Association between circadian and chemotherapeutic cycle effects on plasma concentration of 5‑fluorouracil and the clinical outcome following definitive 5‑fluorouracil/cisplatin‑based chemoradiotherapy in patients with esophageal squamous cell carcinoma". Oncology Letters 17.1 (2019): 668-675.
Chicago
Kuwahara, A., Kobuchi, S., Tamura, T."Association between circadian and chemotherapeutic cycle effects on plasma concentration of 5‑fluorouracil and the clinical outcome following definitive 5‑fluorouracil/cisplatin‑based chemoradiotherapy in patients with esophageal squamous cell carcinoma". Oncology Letters 17, no. 1 (2019): 668-675. https://doi.org/10.3892/ol.2018.9586
Copy and paste a formatted citation
x
Spandidos Publications style
Kuwahara A, Kobuchi S and Tamura T: Association between circadian and chemotherapeutic cycle effects on plasma concentration of 5‑fluorouracil and the clinical outcome following definitive 5‑fluorouracil/cisplatin‑based chemoradiotherapy in patients with esophageal squamous cell carcinoma. Oncol Lett 17: 668-675, 2019.
APA
Kuwahara, A., Kobuchi, S., & Tamura, T. (2019). Association between circadian and chemotherapeutic cycle effects on plasma concentration of 5‑fluorouracil and the clinical outcome following definitive 5‑fluorouracil/cisplatin‑based chemoradiotherapy in patients with esophageal squamous cell carcinoma. Oncology Letters, 17, 668-675. https://doi.org/10.3892/ol.2018.9586
MLA
Kuwahara, A., Kobuchi, S., Tamura, T."Association between circadian and chemotherapeutic cycle effects on plasma concentration of 5‑fluorouracil and the clinical outcome following definitive 5‑fluorouracil/cisplatin‑based chemoradiotherapy in patients with esophageal squamous cell carcinoma". Oncology Letters 17.1 (2019): 668-675.
Chicago
Kuwahara, A., Kobuchi, S., Tamura, T."Association between circadian and chemotherapeutic cycle effects on plasma concentration of 5‑fluorouracil and the clinical outcome following definitive 5‑fluorouracil/cisplatin‑based chemoradiotherapy in patients with esophageal squamous cell carcinoma". Oncology Letters 17, no. 1 (2019): 668-675. https://doi.org/10.3892/ol.2018.9586
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