BACKGROUND Lipoxal is a liposomal oxaliplatin, which reduces the cytotoxic agent's adverse reactions without reducing effectiveness. Our objectives were to determine the adverse reactions, dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) of lipoxal. METHODS Twenty-seven patients with advanced disease of the gastrointestinal system were included in the study. All patients had been pretreated with standard chemotherapy according to established guidelines. At entry, all patients had recurrent or progressive disease (stage IV gastrointestinal cancers: colorectal, gastric and pancreatic). Six lipoxal dose levels (100 mg/m2, 150 mg/m2, 200 mg/m2, 250 mg/m2, 300 mg/m2 and 350 mg/m2) were set and at least 3 patients were included at each level. Eight patients were treated at 300 mg/m2 (MTD). The treatment was given once weekly for 8 weeks. RESULTS No serious side-effects were observed at the first 4 dose levels (100-250 mg/m2). At levels 5 and 6, mild myelotoxicity and nausea were observed. The most common adverse reaction was grade 2-3 peripheral neuropathy, observed in all 4 patients treated at 350 mg/m2. The 350 mg/m2 dose level was therefore considered as DLT and the 300 mg/m2 level as the MTD. Of the 27 patients, 3 achieved partial response and 18 had stable disease for 4 months, (range 2-9 months). CONCLUSIONS The most common toxicity was peripheral neuropathy at the 300 and 350 mg/m2 dose levels. Lipoxal was well-tolerated and greatly reduced all the other side-effects of oxaliplatin, especially myelotoxicity and gastrointestinal tract toxicities. These preliminary results showed adequate effectiveness in pretreated patients.