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Summary: Purpose: This phase II single arm, open label study was designed to evaluate the efficacy and toxicity of oral gefitinib (250mg) daily in previously untreated patients with advanced non-small-cell lung cancer (NSCLC). Methods: Eligible patients had stage IIIB or IV NSCLC with adequate organ functions, and were chemonaïve. All eligible patients were treated with oral administration of 250mg of gefitinib until intolerable toxicity, disease progression or death occurred. Responses were assessed after every 8 weeks of therapy. Results: For a total of 53 patients, the objective response rate (ORR) was 32.1% and overall disease control rate (DCR) was 52.8%. Median overall and progression-free survivals (PFS) were 9.4 (95% CI, 8.8–13.3) and 3.2 months (95% CI, 1.1–5.2) months, and 1-year survival rate was 41.5%. Patients with adenocarcinoma (n =35) had a higher response rate. Adenocarcinoma, female gender (n =24), and response to gefitinib were predictive factors for better survival. The most commonly seen adverse events (AEs) were skin toxicity (54.7%), diarrhea (43.4%) and nail change (16.9%). Most AEs were mild to moderate and considered manageable. Drug-related interstitial pneumonia was clinically diagnosed in four cases (7.5%). Conclusions: Oral gefitinib, as compared to conventional chemotherapy, has comparable effect but less toxicity as a first-line treatment in Chinese patients who have advanced NSCLC, especially in those with adenocarcinoma histology. A further phase III prospective study comparing gefitinib to standard chemotherapy to define the efficacy of gefitinib is appropriate in advanced NSCLC patients. [Copyright &y& Elsevier]

• Our study is the first to evaluate the effect of early thoracic surgery on patients with unresectable stage IIIB–IV EGFR-mutant lung adenocarcinoma who received and responded to EGFR-TKIs. • Thoracic surgery reduced the incidence of death in patients with unresectable stage IIIB–IV EGFR-mutant lung adenocarcinoma who received and responded to EGFR-TKIs. • Thoracic surgery appeared to be more beneficial for OS in older patients (aged ≥65 years) patients receiving and responding to TKIs compared with younger patients. No large-scale, prospective, randomized study has evaluated the effect of thoracic surgery on patients with unresectable stage IIIB–IV epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma who received and responded to EGFR tyrosine kinase inhibitor (TKI) treatment. Therefore, we designed a propensity-score-matched, nationwide, population-based, cohort study to investigate the effects of thoracic surgery on patients with EGFR-mutant lung adenocarcinoma. We included patients with unresectable stage IIIB–IV EGFR-mutant lung adenocarcinoma and categorized them into two groups according to their treatment modalities and compared their outcomes: the case group consisted of patients who underwent thoracic surgery for lung tumors after receiving and responding to EGFR-TKI treatment and the comparison group consisted of patients who received EGFR-TKI treatment alone until tumor progression. Patients in both groups were matched at a ratio of 1:4. The matching process yielded a final cohort of 1395 patients (279 and 1,116 in the case and comparison groups, respectively) who were eligible for further analysis. According to multivariable Cox regression analyses, the adjusted hazard ratio (aHR; 95% confidence interval [CI]) for thoracic surgery for lung tumors after EGFR-TKI use and tumor response (group 2) compared with EGFR-TKI treatment alone (group 1) was 0.445 (0.351–0.564). Thoracic surgery prolonged overall survival in patients with unresectable stage IIIB–IV EGFR-mutant lung adenocarcinoma who received and responded to EGFR-TKI treatment. [ABSTRACT FROM AUTHOR]

Docetaxel has shown activity in the treatment of non-small-cell lung cancer (NSCLC) that has failed previous chemotherapy. Ifosfamide is an active alkylating agent used in the first-line treatment of NSCLC. We conducted a phase II study of docetaxel and ifosfamide chemotherapy in two groups (one with and one without previous paclitaxel treatment) of NSCLC patients who had failed previous chemotherapy, to assess the response and toxicity of this combination chemotherapy. Fifty patients were enrolled from June 2000 to December 2001, including 26 patients treated with paclitaxel-containing agents and 24 patients who had never been treated with paclitaxel. Treatment consisted of docetaxel 60 mg/m2 and ifosfamide 3 g/m2 intravenous infusion on day 1 of every 3 weeks. Two hundred and thirty-eight cycles of treatment were given, with a median of 5 cycles (range, 1–8 cycles). All patients were evaluable for toxicity profile and response rate. The major toxicity was myelosuppression. Grade 3 or 4 neutropenia occurred in 40 patients (80%) during treatment. Febrile neutropenia occurred in 7 patients (14%). Grade 3 anemia occurred in 2 patients. The majority of patients needed a decrease in the treatment dose due to grade 4 or febrile neutropenia. Interstitial pneumonitis occurred in 3 patients, leading to the death of two. Other toxicities were few and mild in severity. After two cycles of treatment, 5 patients (10%) had a partial response (95% confidence interval 1.7–18.3%), including 2 patients previously treated with paclitaxel and 3 who had not received this treatment. More patients who had been previously treated with paclitaxel suffered from progressive disease than among those who had never been treated with paclitaxel (P=0.049). The median time to disease progression was 5 months and the median survival was 8.2 months. Median survival was 7.6 and 8.7 months, respectively, in patients with and without previous paclitaxel treatment (P=0.56). Median survival was 8.7 and 7.6 months in patients receiving docetaxel and ifosfamide as second- and third-line chemotherapy, respectively (P=0.327). In conclusion, docetaxel and ifosfamide salvage chemotherapy produces a relatively low response rate, low dose intensity, and higher proportion of severe neutropenia in NSCLC. Physicians should be alert to the potential of interstitial pneumonitis. Nevertheless, median survival was of a reasonable duration. [Copyright &y& Elsevier]