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Whole-brain radiation fails to boost intracerebral gefitinib concentration in patients with brain metastatic non-small cell lung cancer: a self-controlled, pilot study

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Abstract

Purpose

Whole-brain radiation therapy (WBRT) is generally considered as an efficient strategy to improve blood–brain barrier (BBB) permeability by damaging BBB structure and is therefore, used as a promising pretreatment of chemotherapy. However, the impact of radiotherapy on leaky BBB is still controversial for the reason that BBB of metastatic brain tumor lesion had been breached by tumor metastasizing. Herein, we conducted a self-controlled study to evaluate the effect of WBRT on the permeability of BBB in non-small cell lung cancer (NSCLC) patients with brain metastases (BM).

Method

A prospective self-controlled research was performed. Radiation-naive NSCLC patients with BM were enrolled and treated with gefitinib for 2 weeks, and then concurrently combined with WBRT for 2 weeks. Plasma and cerebrospinal fluid (CSF) before and after WBRT were collected on day 15 and 29 after the initiation of gefitinib treatment. The concentrations of gefitinib in these samples were measured by HPLC.

Results

Three patients were enrolled and evaluated. The concentrations of gefitinib in plasma and CSF pre-WBRT were comparable to those of post-WBRT. Consequently, no significant change was noted in the CSF-to-plasma ratios of gefitinib before and after WBRT (2.79 ± 1.47 vs. 2.35 ± 1.74 %, p = 0.123).

Conclusions

The WBRT may not affect the BBB permeability by determining the concentration of gefitinib in NSCLC patients with BM.

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Acknowledgments

This study was supported by the Zhejiang Cancer Hospital Program for the Cultivation of 1022 Talents (Luo Fang), Zhejiang Provincial Program for the Cultivation of High-level Innovative Heath Talents (Nengming Lin), and Zhejiang Provincial Natural Science Foundation (LY15H310003; Nengming Lin).

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Authors and Affiliations

  1. Laboratory of Clinical Pharmacy, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China

    Luo Fang, Yu Song & Yiwen Zhang

  2. Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus), Hangzhou, Zhejiang, China

    Luo Fang, Xiaojiang Sun & Yaping Xu

  3. Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China

    Xiaojiang Sun & Yaping Xu

  4. College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China

    Fanzhu Li

  5. Department of Radiation Oncology, Affiliated Hangzhou Hospital of Nanjing Medical University, Hangzhou, Zhejiang, China

    Shenglin Ma

  6. Institute for Individualized Medicine, Hangzhou First People’s Hospital, Hangzhou, Zhejiang, China

    Nengming Lin

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  1. Luo Fang
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  2. Xiaojiang Sun
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  3. Yu Song
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Correspondence to Shenglin Ma or Nengming Lin.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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Fang, L., Sun, X., Song, Y. et al. Whole-brain radiation fails to boost intracerebral gefitinib concentration in patients with brain metastatic non-small cell lung cancer: a self-controlled, pilot study. Cancer Chemother Pharmacol 76, 873–877 (2015). https://doi.org/10.1007/s00280-015-2847-z

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  • DOI: https://doi.org/10.1007/s00280-015-2847-z

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