This study was designed to compare high-dose fractionated radiotherapy atone versus the same radiotherapy plus cisplatin in stage III non-small cell lung cancer (NSCLC). We randomly assigned 176 patients with stage III non-small cell lung cancer to one of two treatments; fractionated radiotherapy alone at dose of 64 Gy for 6-7 weeks (2 Gy given 32 times, in five fractions a week) or radiotherapy in the same schedule, combined with 20 mg/m(2) cisplatin 1 h before radiotherapy, given on days 1-5 of the second and sixth treatment weeks. The frequency of loco-regional progression was 68% among the patients who received radiotherapy plus cisptatin and 86% among those who received radiotherapy alone (P = 0.0001). The probability of survival free of disease after 3 years was 10% among the patients assigned to radiotherapy plus cisptatin and 0% among those treated only with radiotherapy (P = 0.0006). Overall survival at 3 years was 10% among those given radiotherapy plus cisptatin and 2% among those who received radiotherapy alone (P = 0.00001). Multivariate analysis demonstrated that radiotherapy plus cisplatin significantly improved loco-regional progression-free survival and overall survival, irrespective of radiation dose. The addition of cisplatin to fractionated radiotherapy prolongs loco-regional progression-free interval and survival in stage III non-small cell lung cancer. (C) 2003 Elsevier Ireland Ltd. All rights reserved.