The CSF penetrations of erlotinib and OSI-420 in patients with NSCLC who had CNS metastases were approximately 5.1% and 5.8%, respectively. This indicates that erlotinib can become a treatment option for CNS metastases of NSCLC.

Recently, two small-molecule kinase inhibitors targeting epidermal growth factor receptor have proven effective in the treatment of non-small cell lung cancer. There are specific activating mutations within the tyrosine kinase domain of epidermal growth factor receptor related to the sensitivity of tyrosine kinase inhibitors. However, it is unknown whether rare mutations in the N-lobe (exons 18-20) and the C-lobe (exon 21) of the epidermal growth factor receptor kinase domain other than L858R in exon 21 and the in-frame deletion in exon 19 may predict the effectiveness of epidermal growth factor receptor-tyrosine kinase inhibitors. We reported a case of non-small cell lung cancer harboring a rare epidermal growth factor somatic mutation, codon 768 AGC > ATC in exon 20 (S768I), who showed a good clinical response to gefitinib. Therefore, we may suggest that this rare mutation (S768I in exon 20) may not be an insensitive epidermal growth factor receptor somatic mutation in vivo.

Polymorphisms have been identified in the vascular endothelial growth factor (VEGF) gene that may affect VEGF production. We hypothesized that such polymorphisms may correlate with survival outcomes among advanced-stage non-small-cell lung cancer (NSCLC) patients. We evaluated the association between VEGF polymorphisms and overall survival among patients with advanced NSCLC who were treated with at least one cytotoxic regimen at

Erlotinib was hardly affected by renal function and HD, which confirms the effectiveness and safety of erlotinib treatment in patients with NSCLC and CRF undergoing HD. Erlotinib can become one treatment option for such patients.

Purpose: We examined patients with advanced nonsquamous, non-small cell lung cancer (NSCLC) to evaluate epidermal growth factor receptor (EGFR) mutation status and serum C-reactive protein (CRP) for their associations with response to gefitinib therapy and for prognostic impacts. Methods: Serum levels of CRP from 79 Japanese patients with advanced nonsquamous NSCLC were measured before the start of gefitinib. We used the peptic nucleic acid-locked nucleic acid clamp method to determine their EGFR somatic mutation status. We evaluated the relationship between each independent clinicopathological variable and the response to gefitinib therapy and the risk factors associated with prognosis. Results: Having CRP-positive serum and having wild-type EGFR were both independent negative predictive factors for the response to gefitinib treatment by multivariate logistic regression model analysis. Having CRP-positive serum and having wild-type EGFR were significant independent negative prognostic factors for survival based on multivariate analysis. Conclusions: Having CRP-positive serum predicted a lack of response to gefitinib therapy independent of EGFR mutational status. Both CRP-positive serum and wild-type EGFR were independent poor prognostic factors in patients with nonsquamous NSCLC who received gefitinib therapy.