The toxicity of escalating doses of liposome-complexed mitoxantrone (LCM) was evaluated in 22 women with histological/cytological diagnosis of metastatic breast cancer (21 pts) or adenocarcinoma of unknown primary origin (1 pt). All patients but one had been pretreated with chemotherapy. LCM was given IV as a 1h-infusion, repeated every 3 weeks, from a starting dose of 3 mg/m2, corresponding to 1/3 of the MELD10. An intra-patient dose escalation scheme, with an increase per cycle of 3 mg/m2 up to 12 mg/m2, and then by 2 mg/m2 was applied, treatment being continued until tumour progression, or toxicity, or up to a maximum of 6 cycles, whichever occurred first. Granulocytopenia was dose-limiting, with a GNC count of less than 0.5 x 10(3)/microliters after 30%, 28%, 50% and 50% of the cycles given at 16, 18, 20 and 22-24 mg/m2, respectively. The lowest GNC count occurred usually 2 weeks after treatment, with recovery in the following week. Gastro-intestinal toxicity, mucositis and alopecia were rare and of mild degree. Two patients, with a subtotal neoplastic involvement of the liver and a pretreatment grade 4 liver impairment, died because of acute liver failure a few days after treatment. The maximum tolerable dose was defined at 22 mg/m2 and 18 mg/m2, given every 3 weeks for 6 cycles, was the regimen recommended for phase II studies. Seven previously untreated patients with metastatic breast cancer have been so far treated. The pattern of toxicity of LCM (specific, short-lasting granulocytopenia; negligible, non cumulative non hematological toxicity) was confirmed.(ABSTRACT TRUNCATED AT 250 WORDS)