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A phase II study of icotinib and whole-brain radiotherapy in Chinese patients with brain metastases from non-small cell lung cancer

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Abstract

Purpose

Icotinib is a new first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. A phase II study was conducted to evaluate the efficacy and safety of icotinib in combination with whole-brain radiotherapy (WBRT) in Chinese NSCLC patients with brain metastases (BMs); the cerebrospinal fluid (CSF)/plasma concentrations of icotinib were also investigated.

Methods

Eligible patients had BMs from NSCLC, regardless of the EGFR status. Icotinib was administered at 125 mg orally 3 times/day until tumor progression or unacceptable toxicity, concurrently with WBRT (3.0 Gy per day, 5 days per week, to 30 Gy). CSF and plasma samples were collected simultaneously from 10 patients. Icotinib concentrations in the CSF and plasma were measured by high-performance liquid chromatography coupled with tandem mass spectrometry.

Results

Twenty patients were enrolled. The median follow-up time was 20.0 months. The overall response rate was 80.0 %. The median progression-free survival time was 7.0 months (95 % CI 1.2–13.2 months), and the median survival time (MST) was 14.6 months (95 % CI 12.5–16.7 months). Of the 18 patients with known EGFR status, the MST was 22.0 months for those with an EGFR mutation and was 7.5 months for those with wild-type EGFR (P = 0.0001). The CSF concentration and penetration rate of icotinib were 11.6 ± 9.1 ng/mL and 1.4 ± 1.1 %, respectively. No patient experienced ≥grade 4 toxicity.

Conclusions

Icotinib was well tolerated in combination with WBRT and showed efficacy in patients with BMs from NSCLC. This clinical benefit was related to the presence of activating EGFR mutations.

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Authors and Affiliations

  1. Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology (Esophagus, Lung), Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou, 310022, Zhejiang, People’s Republic of China

    Yun Fan, Zhiyu Huang, Luo Fang, Lulu Miao, Lei Gong, Haifeng Yu, Haiyan Yang, Tao Lei & Weimin Mao

Authors
  1. Yun Fan
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  2. Zhiyu Huang
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  3. Luo Fang
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  4. Lulu Miao
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  5. Lei Gong
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  6. Haifeng Yu
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  7. Haiyan Yang
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  8. Tao Lei
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  9. Weimin Mao
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Correspondence to Weimin Mao.

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Fan, Y., Huang, Z., Fang, L. et al. A phase II study of icotinib and whole-brain radiotherapy in Chinese patients with brain metastases from non-small cell lung cancer. Cancer Chemother Pharmacol 76, 517–523 (2015). https://doi.org/10.1007/s00280-015-2760-5

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  • DOI: https://doi.org/10.1007/s00280-015-2760-5

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