Blood-brain barrier permeability of gefitinib in patients with brain metastases from non-small-cell lung cancer before and during whole brain radiation therapy
| Autor: | Fei Xu, Shu Xiang Ma, Hai Liao, Jian Zhong Liang, Xiao Xiao Dinglin, Li Kun Chen, Tao Qin, Yin Duo Zeng, Li Zhang, Wei Dong Wei |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Oncology
Adult Male medicine.medical_specialty Lung Neoplasms gefitinib Antineoplastic Agents blood brain barrier Young Adult Gefitinib Internal medicine Carcinoma Non-Small-Cell Lung medicine Humans In patient brain metastasis whole brain radiation therapy Neoplasm Metastasis Lung cancer skin and connective tissue diseases neoplasms Aged business.industry Brain Neoplasms Cancer Middle Aged medicine.disease Prognosis Surgery respiratory tract diseases Blood-Brain Barrier Quinazolines Female Blood brain barrier permeability Non small cell Clinical Research Paper Whole brain radiation therapy business Non-small-cell lung cancer Brain metastasis medicine.drug |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // 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 1 Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China 2 Lab of Phase I Clinical Study, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China 3 Department of Breast Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China 4 Department of Pathology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China 5 Department of Medical Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China * These authors have contributed equally to this work Correspondence to: Li-kun Chen, e-mail: chenlk@sysucc.org.cn Keywords: Non-small-cell lung cancer, brain metastasis, gefitinib, whole brain radiation therapy, blood brain barrier Received: December 10, 2014 Accepted: January 23, 2015 Published: February 06, 2015 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|