PURPOSE: To evaluate new drugs in combination with cisplatin in unresectable stage III non-small-cell lung cancer, Cancer and Leukemia Group B (CALGB) conducted a randomized phase II study of two cycles of induction chemotherapy followed by two additional cycles of the same drugs with concomitant radiotherapy. PATIENTS AND METHODS: Eligible patients received four cycles of cisplatin at 80 mg/m(2) on days 1, 22, 43, and 64 with arm 1: gemcitabine 1,250 mg/m(2) on days 1, 8, 22, and 29 and 600 mg/m(2) on days 43, 50, 64, and 71; arm 2: paclitaxel 225 mg/m(2) for 3 hours on days 1 and 22 and 135 mg/m(2) on days 43 and 64; and arm 3: vinorelbine 25 mg/m(2) on days 1, 8, 15, 22, and 29 and 15 mg/m(2) on days 43, 50, 64, and 71. Radiotherapy was initiated on day 43 at 2 Gy/d (total dose, 66 Gy). RESULTS: One hundred seventy-five eligible patients were analyzed. Toxicities during induction chemotherapy consisted primarily of grade 3 or 4 granulocytopenia. Grade 3 or 4 toxicities during concomitant chemoradiotherapy consisted of thrombocytopenia, granulo-cytopenia, and esophagitis. Response rates after completion of radiotherapy were 74%, 67%, and 73% for arms 1, 2, and 3, respectively. Median survival for all patients was 17 months. One-, 2-, and 3-year survival rates for the patients on the three arms were 68%/37%/28%, 62%/29%/19%, and 65%/40%/23%. CONCLUSION: Four cycles of gemcitabine, vinorelbine, or paclitaxel in combination with cisplatin can be administered at these doses and schedules. The observed survival rates exceed those of previous CALGB trials and may be attributable to the use of concomitant chemoradiotherapy. Induction chemotherapy added to concomitant chemoradiotherapy is being evaluated in a phase III randomized trial.