Abstract

Background. Although epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are effective in patients with nonsmall cell lung cancer with epidermal growth factor receptor (EGFR) mutation, EGFR-TKIs have a risk of inducing fatal interstitial lung disease (ILD). The selection of chemotherapy based on the EGFR mutation status is recommended, however, the frequency of EGFR mutation in patients with ILD and the efficacy and safety of EGFR-TKI in patients with ILD and EGFR mutation are unknown. Methods. We retrospectively reviewed the association of the EGFR mutation status of nonsmall cell lung cancer and pulmonary diseases. Based on high-resolution computed tomography (HRCT) performed at diagnosis of lung cancer, patients were categorized into three groups: normal, emphysema, and fibrosis. Results. Of 198 patients with nonsmall cell lung cancer, we identified 52 (26.3%) patients with an EGFR mutation. EGFR mutations were identified in 43 (35.2%) of 122 patients with normal lungs, 8 (13.6%) of 59 with emphysema, and 1 (5.9%) of 17 with pulmonary fibrosis. Of the 52 patients with EGFR mutation, 43 patients received gefitinib. One patient with an EGFR mutation and fibrosis developed fatal ILD. There was not a significant difference in median overall survival from gefitinib treatment between never-smokers and smokers (797 days versus not reached; P = 0.96). Conclusions. Patients with sensitive EGFR mutation and normal lungs may benefit from an EGFR-TKI treatment even if they have smoking history.

Highlights

  • Gefitinib is a reversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) used for the treatment of nonsmall cell lung cancer patients [1]

  • Demographic and clinical factors such as East-Asian race, female gender, nonsmoking status, and adenocarcinoma were shown to be predictive of the efficacy of gefitinib, two pivotal studies showed that the presence of somatic mutations in the kinase domain of epidermal growth factor receptor (EGFR) strongly correlates with increased responsiveness to EGFRTKIs in patients with nonsmall cell lung cancer [2, 3]

  • We reviewed 198 patients who were examined for EGFR mutation status and assessed the association of EGFR mutations with the underlying pulmonary diseases on chest high-resolution computed tomography (HRCT)

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Summary

Introduction

Gefitinib is a reversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) used for the treatment of nonsmall cell lung cancer patients [1]. It was later found that the subgroups of patients with nonsmall cell lung cancer who had sensitivity to gefitinib had a high incidence of EGFR mutations [4, 5]. First-line gefitinib for patients with advanced nonsmall cell lung cancer who are selected on the basis of EGFR mutations improves progression-free survival, with acceptable toxicity, compared with standard chemotherapy, it failed to prolong overall survival [6, 7]. We retrospectively reviewed the association of the EGFR mutation status of nonsmall cell lung cancer and pulmonary diseases. Patients with sensitive EGFR mutation and normal lungs may benefit from an EGFR-TKI treatment even if they have smoking history

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