Aviscumine is a ribosome-inactivating protein with potent antitumour activity in vitro and in vivo and is an Escherichia coli-derived recombinant counterpart of natural mistletoe lectin-I. The current study was performed to determine the safety profile, dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of a prolonged infusion of aviscumine in cancer patients. Aviscumine was given once weekly as a 24 h central intravenous infusion in patients with advanced, refractory progressive solid malignant tumours. Fourteen fully eligible patients (11 male, 3 female) with a median age 58 yrs (range 41-77) were enrolled. They had histologically verified disease, were 18 yrs old, had an ECOG PS 2 and adequate bone marrow, liver and renal function. DLT was defined as any non-haematological grade 3-4 toxicity (Common Toxicity Criteria [CTC] version 2.0), neutrophil count <500/ microl for 7 days, febrile neutropenia or thrombocytopenia grade 4. The MTD was defined as the dose level below the dose at which 2 patients per dose level experienced a DLT during the first treatment cycle. Colorectal cancer, soft tissue sarcoma and pancreatic cancer were the most common tumour types. Dose levels of aviscumine ranged from 4 to 6 microg/kg. The median number of cycles was 2.8 (range, 2-8). Common side effects in cycle 1 were fatigue, fever, nocturia, urticaria, erythema and pruritus. DLTs occurred in 2/3 patients on the 6 microg/kg dose level and consisted of increases in ASAT grade 3, ALAT grade 3, gammaGT grade 3/4, hypokalemia grade 3 and fatigue grade 3. No DLTs were observed on dose levels 4 and 5 microg/kg. The best response (RECIST) was stable disease in 4 pts, lasting for 4-8 cycles. Pharmacokinetics indicated that potentially active plasma levels of the compound were maintained during the entire infusion. We conclude that the recommended dose for weekly 24 h infusions of Aviscumine should be 5 microg/kg.