18028 Background: Lipoplatin is a liposomal formulation of cisplatin, designed to reduce its adverse reactions without reducing efficacy. Its nanoparticles evade immune surveillance and extravasate preferentially into tumors inducing tumor cell apoptosis; lipoplatin may also act as antiangiogenesis factor. This is the initial report of a randomized, multicenter, phase III trial comparing the two drugs. Methods: Eligibility criteria included confirmed diagnosis of inoperable/metastatic NSCLC, no previous chemotherapy, WHO PS 0–1, adequate end-organ function. Patients received Lipoplatin 120 mg/m2 D1,8,15 or cisplatin 100 mg/m2 D1, combined with gemcitabine 1,000 mg/m2 D1,8, in 3-week cycles, with disease evaluation after 3 and 6 cycles. Primary endpoints are overall survival and toxicity, with Response Rates, PFS and QOL also being evaluated. Results: 59 patients have been treated, 33 with lipoplatin and 26 with cisplatin; 17 have completed treatment. 2 lipoplatin patients had a hypersensitivity reaction during the first infusion. There were no grade 4 toxicities. Grade 3 toxicities were observed in <5% of the patients and were comparable for the two groups, except neutropenia (3% for lipoplatin, 15% for cisplatin). Main grade 1–2 toxicities were anemia (93% vs 88%), leucopenia (51% vs 38%), neutropenia (45% vs 30%), thrombocytopenia (58% vs 31%), hepatotoxicity (38% vs 46%), nausea/vomiting (13% vs 35%), asthenia (31% vs 30%) and anorexia (32% vs 34%). Concerning nephrotoxicity, grade 2 was reported in only 6% of lipoplatin patients vs 19% in cisplatin, although lipoplatin was administered without pre-hydration as a 6-hour infusion. Neurotoxicity was also markedly less in lipoplatin. So far, 32 patients have been assessed for response, 16 in each group; 4 partial responses have been reported in each group. However, difference has been observed in stable disease (23% in lipoplatin vs 12% in cisplatin) as well as progressive disease (16% vs 35%). Conclusions: Preliminary results show that lipoplatin may have a better safety and therapeutic profile than cisplatin, when combined with gemcitabine, in advanced NSCLC. Particularly important might be its significantly lower neuro- and nephro-toxicity and its administration on an outpatients basis. No significant financial relationships to disclose.