Purpose: This is a phase I/II a study to assess tolerance of gemcitabine and paclitaxel with radiotherapy in locally advanced non-small-cell lung cancer after induction chemotherapy. Patients and Methods: Fifty-seven patients with stage III non-small-cell lung cancer were treated with cisplatin 80 mg/m 2 on days 1 and 22 and gemcitabine 1,250 mg/m2 on days 1, 8, 22, and 28. Chemoradiotherapy began on day 43 as follows: cohort 1 (n = 9), gemcitabine 300 mg/m2 and paclitaxel 35 mg/m2 weekly (except week 9); cohort 2 (n = 9), gemcitabine 150 mg/m2 and paclitaxel 35 mg/m2 weekly (except week 9); cohort 3 (n = 10) and the 25 phase Na patients, gemcitabine 300 mg/m2 and paclitaxel 135 mg/m2 every 21 days. Patients were treated with three-dimensional thoracic radiotherapy concurrently to 60 Gy. Results: Weekly chemotherapy resulted in grade 4 esophageal and grade 3 or higher pulmonary toxicities. Reduction in dose density (cohort 3) led to a tolerable toxicity profile and was chosen as the phase IIa regimen. The response rate to induction was 49%, with stable disease in 40% of the patients. The response rate after consolidation therapy was 75% (94% for weekly chemotherapy v82% for every 3 weeks). Median survival was 23 months, and 3-year survival was 45% for eligible patients. Local relapse occurred in 20% of the patients. Performance status of more than 1 predicted for poor outcome, but baseline pulmonary function did not. Dosimetric parameters including V15, V20, V30 (percent lung volume receiving ≥ 15, ≥ 20, and ≥ 30 Gy, respectively), and mean lung dose correlated with pulmonary toxicity. Conclusion: Additional investigation with the 3-week schedule is warranted in patients with a good performance status based on the safety profile and preliminary efficacy data observed in this study. © 2005 by American Society of Clinical Oncology.