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.. In these 4 randomized phase III trials, severe adverse events or treatment-related toxicity leading to discontinuation of the therapy were significantly less prevalent in patients treated A-769662 manufacturer with first-generation EGFR-TKIs compared to standard chemotherapy. The most common adverse events in patients treated with first-generation EGFR-TKIs were cutaneous toxicity, including skin rash and dry skin, diarrhea and elevated transaminase level. Compared to chemotherapy, hematological toxicity, fatigue, alopecia and nausea were less prevalent in the experimental arm of first-generation EGFR-TKIs[9-12]. Quality of life Three randomized phase III trials comparing first-generation EGFR-TKIs to standard chemotherapy have shown EGFR-TKI to be superior to chemotherapy in quality of life (QoL) effects. Two randomized phase III trials buy Cilengitide of first-generation EGFR-TKIs, including the IPASS study[7] and OPTIML study[13], assessed QoL as a secondary endpoint using Functional Assessment of Cancer Therapy-Lung (FACT-L), Trial Outcome Index (TOI), or Lung Cancer-Specific Subscale (LCS; Table ?Table2).2). Patients receiving first-line EGFR-TKIs experienced clinically relevant improvements in QoL compared to patients treated with standard platinum doublet chemotherapy in these studies. Among patients harboring activating EGFR mutations in the IPASS study, significant improvement of QoL was found in patients treated with gefitinib compared to patients treated with chemotherapy. Furthermore, rapid improvement of QoL both in terms of FACT-L and LCS was observed in patients with mutated EGFR. In the OPTIMAL study, patients with an improvement in QoL showed improved PFS compared with patients with stable or worsened QoL. Further signi?cant Wrch1 correlations were observed between improved QoL and tumor response with FACT-L, TOI and LCS. Table 2 Quality of life assessment (first-generation epidermal growth factor receptor-tyrosine kinase inhibitors vs chemotherapy) In the NEJ 002 study, QoL was assessed by analyzing time to deterioration from baseline in the physical, mental and life well-being QoL scales. Time to defined deterioration in physical and life well-being significantly favored gefitinib over standard chemotherapy [hazard ratio (HR) of time to deterioration, 0.34; 95% confidence interval (CI), 0.23-0.50; P