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. 2015 Apr 10;6(10):8366-76.
doi: 10.18632/oncotarget.3187.

Blood-brain barrier permeability of gefitinib in patients with brain metastases from non-small-cell lung cancer before and during whole brain radiation therapy

Yin-Duo Zeng  1 , Hai Liao  2 , Tao Qin  1 , Li Zhang  1 , Wei-Dong Wei  3 , Jian-Zhong Liang  4 , Fei Xu  1 , Xiao-Xiao Dinglin  5 , Shu-Xiang Ma  1 , Li-Kun Chen  1
Affiliations

Blood-brain barrier permeability of gefitinib in patients with brain metastases from non-small-cell lung cancer before and during whole brain radiation therapy

Yin-Duo Zeng et al. Oncotarget. .

Abstract

Introduction: To explore the ability of gefitinib to penetrate blood brain barrier (BBB) during whole brain radiation therapy (WBRT).

Patients and methods: Enrolled in this study were eligible patients who were diagnosed with BM from NSCLC. Gefitinib was given at 250 mg/day for 30 days, then concurrently with WBRT (40 Gy/20 F/4 w), followed by maintenance. Serial CSF and blood samples were collected on 30 day after gefitinib administration, and at the time of 10, 20, 30 and 40 Gy following WBRT. CSF and plasma samples of 13 patients without BM who were treated with gefitinib were collected as control. CSF and plasma gefitinib levels were measured by LC-MS/MS.

Results: Fifteen BM patients completed gefitinib plus WBRT. The CSF-to-plasma ratio of gefitinib in patients with BM was higher than that in patients without BM (1.34% vs. 0.36%, P < 0.001). The CSF-to-plasma ratio of gefitinib increased with the increased dose of WBRT and reached the peak (1.87 ± 0.72%) at 30 Gy, which was significantly higher than that 1.34 ± 0.49% at 0 Gy (P = 0.01). The median time to progression of brain lesions and the median overall survival were 7.07 and 15.4 months, respectively.

Conclusion: The BBB permeability of gefitinib increased in accordance with escalated dose of WBRT.

Keywords: blood-brain barrier; brain metastasis; gefitinib; non-small-cell lung cancer; whole brain radiation therapy.

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Conflict of interest statement

DISCLOSURE OF CONFLICT OF INTEREST

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1. Disposition of patients (CONSORT diagram)
Figure 2
Figure 2
(A) Correlation between plasma and CSF concentrations of gefitinib in 15 patients with BM. A good correlation (R2 = 0.57) was demonstrated (P = 0.001). (B) Correlation between plasma and CSF concentrations of gefitinib in 13 patients without BM. A good correlation (R2 = 0.70) was demonstrated (P = 0.004).
Figure 3
Figure 3. Gefitinib CSF concentration (A) and CSF-to-plasma ratio of gefitinib concentration (B) during WBRT compared with that of baseline (0 Gy)
*P < 0.05.
Figure 4
Figure 4. Comparison of overall survival (A) and progression-free survival (B) between patients with BM from NSCLC according to EGFR mutation status
Comparison of time to progression of brain lesions (C) and lung lesions (D) from patients with BM from NSCLC according to EGFR mutation status.
See this image and copyright information in PMC

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