Head and neck irradiation modulates pharmacokinetics of 5-fluorouracil and cisplatin

Journal of Translational Medicine

Yu-Jen Chen⁴  Tung-Hu Tsai²  Li-Ying Wang⁵  Hui-Ju Tien⁷  Hung-Chi Tai⁶  Meng-Hsuan Chiang³  Mei-Ling Hou³  Chen-Hsi Hsieh¹ 

[1] Department of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan;Department of Education and Research, Taipei City Hospital, Taipei, Taiwan;Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, 155, Li-Nong Street Section 2, Taipei 112, Taiwan;Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan;School and Graduate Institute of Physical Therapy, College of Medicine, National Taiwan University, Taipei, Taiwan;Department of Radiation Oncology, Mackay Memorial Hospital, 92, Chung-Shan North Road, Taipei, Taiwan;Division of Radiation Oncology, Department of Radiology, Far Eastern Memorial Hospital, Taipei, Taiwan

关键词: Radiotherapy;    Pharmacokinetics;    Head and neck;    Concurrent chemoradiation therapy (CCRT);    Cisplatin (CDDP);    5-Fluorouracil (5-FU);   

Others  :  826303
DOI  :  10.1186/1479-5876-11-231

 received in 2013-05-02, accepted in 2013-09-10,  发布年份 2013

【 摘 要 】

Background

5-fluorouracil (5-FU) and cisplatin (CDDP) are used to enhance radiotherapy (RT) effect for head and neck (HN) cancers. However, the effect of local RT on systemic chemotherapeutics remains unclear. Here, we evaluated the influence of HN irradiation on the pharmacokinetics (PK) of 5-FU and CDDP in rats as experimental model.

Methods

The radiation dose distributions of HN cancer patients were determined for the low dose areas, which are generously deposited around the target volume. Two Gy and 0.5 Gy RT were selected. Single-fraction radiation was delivered to the HN of Sprague–Dawley rats. 5-FU at 100 mg/kg or CDDP at 5 mg/kg was intravenously infused 24 hours after radiation.

Results

Radiation at 2 Gy reduced the area under the plasma concentration vs. time curve (AUC) of 5-FU and CDDP by 16% and 29% compared to non-irradiated controls, respectively. This was accompanied by incremental total plasma clearance values. Intriguingly, low dose radiation at 0.5 Gy resulted in a similar pharmacokinetic profile, with a 17% and 33% reduction in the AUC of 5-FU and CDDP, respectively. The changes in AUC of bile, which increases with RT, were opposite to AUC of plasma for both drugs.

Conclusions

The local HN RT could modulate systemic PK of 5-FU and CDDP in rats. This unexpected RT-PK phenomena may provide a reference for adjustment of drug administration and is worthy of further investigation.

Trial registration

ClinicalTrials.gov ID NCT01755585 and NCT01609114

【 授权许可】

   
2013 Hsieh et al.; licensee BioMed Central Ltd.

【 图 表 】

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