Many patients with stage IV nonsmall cell lung cancer (NSCLC) are unfit for cisplatin-based chemotherapy because of poor performance status, impaired renal function or severe comorbidity. We documented the feasibility of a combination of weekly vinorelbine and biweekly oxaliplatin in a population of stage IV NSCLC patients unable to receive cisplatin. Fifty-five chemo-naive patients (40 males, median age 60 years, range 43-84) were treated on an outpatient basis, and received every 2 weeks: vinorelbine 25 mg/m intravenously on day 1 and 60 mg/m orally on day 8, and oxaliplatin 85 mg/m intravenously on day 1. Patients were considered unfit for cisplatin because of performance status > or =2 (30 patients), impaired renal function (17 patients) or severe comorbidities (eight patients). Twenty-two patients (40%) had two or more metastatic sites, and 14 (25%) had central nervous system metastases. A total of 288 cycles were given (median per patient: 4, range 1-11). The planned dose intensity of vinorelbine was administered in 65% of patients. One complete and 13 partial responses were observed, providing an objective response rate of 26% (95% confidence interval: 14.4-37.6). The median progression-free survival and overall survival were 3.5 months and 9.5 months, respectively. The 1-year survival rate was 24% (95% confidence interval: 12.7-35.3). The main grade 3/4 toxicities were: neutropenia (15 patients, 27%), anaemia (12 patients, 22%) and peripheral neuropathy (eight patients, 15%). Three patients (5.5%) experienced febrile neutropenia. In a nonselected NSCLC patient population, the vinorelbine-oxaliplatin doublet had clinical activity in the same range as cisplatin-based combinations. This doublet allows combining a platinum derivative with a sustained dose intensity of vinorelbine in unfit patients.