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Introduction This study was aimed at comparing the efficiency and tolerability of two reference protocols Cisplatin and Etoposide and Cisplatin and Vinorelbine in advanced Non-Small Cell Lung Cancer. Material and Methods A total of 60 patients (two groups consisting of 30 patients) were treated for advanced Non-Small Cell Lung Cancer during the period from January to December 2005 according to the reference protocols (Cisplatin 100mg/m² D1; Vinorelbine 30 mg/m² D1, D8 on 4 weeks) and (Cisplatin 100 mg/m² D1; Etoposide 100 mg/m² D1, D3, D5 on 4 weeks) at the Department of Oncology of KBC "Bežanijska kosa". All patients were analysed for tumour response, progression free survival as well as for toxicity. X² test, Kaplan Meiers curves and Log rank test were used for statistical analysis. Results Although the recorded response rates were a bit lower than in previously published trials, they were not significantly different p=0.485. No statistically significant difference was recorded in either progression free survival or overall survival. The chemotherapeutical Cisplatin/Etoposide protocol proved to be more toxic both in hematologic (3% vs. 10%) and total toxicities (p=0.047). Conclusion Our study proved both protocols to have equivalent efficacy. However, the Cisplatin, Vinorelbine protocol could be recommended because of its less expressed toxic effects. [ABSTRACT FROM AUTHOR]