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Fan Y.,Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology Esophagus | Huang Z.,Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology Esophagus | Fang L.,Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology Esophagus | Miao L.,Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology Esophagus | And 5 more authors.
Cancer Chemotherapy and Pharmacology | Year: 2015

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. © 2015 Springer-Verlag Berlin Heidelberg. Source


Fan Y.,Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology Esophagus | Huang Z.,Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology Esophagus | Fang L.,Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology Esophagus | Miu L.,Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology Esophagus | And 5 more authors.
OncoTargets and Therapy | Year: 2013

Background: Chemotherapy and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are controversial in the treatment of patients with brain metastases from non-small-cell lung cancer (NSCLC). Methods: We retrospectively studied the effects of solely localized treatment or localized treatment in combination with chemotherapy and/or EGFR tyrosine kinase inhibitors on outcomes in 210 NSCLC patients with brain metastases. The effects of treatment modality, Karnofsky performance status, age, primary tumor histology, number of brain metastases, and other factors on survival time were analyzed, and the robustness of two prognostic indices, ie, recursive partitioning analysis and graded prognostic assessment, was evaluated. Results: The median survival time in patients with systemic medication and localized treatments was higher than in those with localized treatments alone (11 versus 3 months, P=0.000). Within the systemic medication group, median survival time was significantly longer for EGFR tyrosine kinase inhibitors than for other types of chemotherapy (12 versus 9 months, P=0.002). In the EGFR tyrosine kinase inhibitor group, median survival time for patients with EGFR gene mutation was 20 months versus 8 months for those with the wild-type EGFR gene. The median survival time with pemetrexed was significantly higher than with other chemotherapies (13 versus 7 months, P=0.006). In multivariate analysis, the prognosis was significantly correlated with treatment modality (P=0.000), Karnofsky performance status (P=0.000), number of brain metastases (P=0.001), and histologic tumor type (P=0.007). In the graded prognostic assessment model, survival curves for the subgroups showed clear separations. Conclusion: NSCLC patients with brain metastasis benefited from pemetrexed and/or tyrosine kinase inhibitors along with localized treatments, and the graded prognostic assessment index is a robust model for prognostic evaluation. © 2013 Fan et al. Source

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