Cases who received anti-EGFR TKI treatment were retrieved. Anti-EGFR treatment Anti-EGFR treatment
was introduced to NSCLC patients who had clinical stage IIIB, stage IV, or recurrent disease, and a measurable indicator Selleckchem JIB04 lesion by RECIST classification that had not been irradiated. Patients could have received any number of prior chemotherapy regimens and 3 weeks must have elapsed since prior chemotherapy. Eligible patients had Karnofsky performance status (PS) ≥60% or ECOG PS ≥2, sufficient bone marrow function and adequate liver and kidney function. Patients with brain metastases stable for >3 months were also candidates for such treatment. All patients’ signed informed consent before starting treatment. Patients EPZ-6438 mouse must have been treated with either single agent gefitinib or erlotinib. Availability of paraffin-embedded tissue sample at diagnosis was also classified as an entry criterion for this study. All patients signed informed consent for the use of biological materials for research purposes. The study was conducted according selleck kinase inhibitor to the Declaration of Helsinki and the guidelines for Good Clinical Practice. The bioethics Committee of Metropolitan
Hospital approved the study and the collection of biological material. Patient evaluation and treatment All patients received gefitinib at 250 mg per day orally or erlotinib at 150 mg orally. Gefitinib was supplied free of charge by AstraZeneca as part of an international compassionate use program. Since 2005 erlotinib was nationally approved for the treatment of NSCLC irrespective of EGFR mutational status. Treatment was administered daily with a treatment cycle constituting 28 days. Treatment was discontinued for up to 7 days for grade 3–4 toxicity, until resolution of toxicity to ≤1. For non-resolving toxicities of
more than 15 days, treatment was ceased. Treatment was continued until disease progression, serious adverse toxicity, at the decision of the treating physician, PD184352 (CI-1040) or following voluntary patient withdrawal. Patients were eligible for response evaluation after completion of >2 months treatment. Clinical data including smoking history, clinical stage, pathological diagnosis and response data for all patients was retrieved from their medical reports. Somatic mutation analyses Genomic DNA was extracted from paraffin embedded tumors obtained retrospectively from HeCOGs Tumor Repository Bank, as previously described. All paraffin blocks were examined on H&E for histological verification according to W.H.O [19]. Tumors with >75% neoplastic cell content (%NCC) were considered as eligible for analysis. For biopsies with inadequate %NCC, macro-dissection on 5 μm sections was performed to increase the content to >75%. Mutational analysis for all genes was conducted as previously described [20]. The primer sequences for all reactions are available upon request. All studied exons were confirmed, for EGFR.