Several Canadian centers are studying the favorable activity and toxicity profile of vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Médicament, Paris, France) in current and future trials of adjuvant and neoadjuvant treatment of non-small cell lung cancer. In locally advanced, unresectable disease, the 10-week regimen in cisplatin 100 mg/m2 during weeks 1 and 5, vinorelbine 30 mg/m2 weekly for 5 weeks with a 50% dose reduction planned for week 2 only, and accelerated fractionation thoracic irradiation during weeks 7 to 10 (30 fractions of 2 Gy in 4 weeks, once daily during weeks 7 and 8, and twice daily during weeks 9 and 10). Preliminary data on 17 patients who have completed treatment to date show it has been well tolerated, with only four cases of grade 3 nonhematologic toxicities. Favorable results from combined therapy with cisplatin and vinorelbine in advanced disease have led the National Cancer Institute of Canada Clinical Trials Group to consider testing adjuvant cisplatin and vinorelbine in completely resected non-small cell lung cancer. Surgically staged patients with T2, N0 and T1-2N1 tumors will be stratified according to nodal status and presence or absence of ras oncogene mutations in resected tumor DNA. Patients will be randomized to observation or a 16-week trial of adjuvant chemotherapy with cisplatin 50 mg/m2 days 1 and 8 every 4 weeks during the 16 weeks, and vinorelbine 30 mg/m2 weekly for 16 weeks. All resected tumors will be banked for further correlative studies to identify a clinically meaningful panel of molecular prognostic markers.