Despite improvements in chemotherapy of advanced and metastatic Non-Small-Cell-Lung-Cancer (NSCLC) the prognosis of these patients still remains poor with a 5-year-survival of 2 to 5 %. Due to the high level of hypoxic cells in solid tumors agents with activity in hypoxic milieu as the Benzotriazine compound Tirapazamine (SR 259 075) might improve the therapeutic results. We treated 45 patients with advanced or metastatic Non-Small-Cell-Lung-Cancer (stage IIIb: 20 patients, stage IV: 25 patients) with the combination TPZ 330 mg/m (2) (day 1), Cisplatin 75 mg/m (2) (day 1) and Gemcitabine 1250 mg/m (2) (day 1 and 8) every 3 weeks. With a response rate of 40 % median progression free survival was 6.7 months (4.8 - 8.1 months) and median survival was 8.1 months (7.5 - 12.5 months), (1-year-survival: 35 %). Hematologic and non-hematologic toxicity was moderate (neutropenia CTC grade 3 and 4: 20 %, thrombocytopenia CTC grade 3 and 4: 16 %, nausea and vomiting CTC 3: 5 %). Treatment of advanced and metastatic NSCLC with TPZ in combination with Gemcitabine/Cisplatin was well feasible and showed results recording to currently published data. The results of a following phase III-trial are awaited.