Advanced breast cancer remains a major clinical problem. Current chemotherapy regimens are able to induce a clinical response in many patients but do not appear to influence significantly patients' survival. The use of new drugs such as mitoxantrone with a predicted lower toxicity and biochemical modulation of 5-fluorouracil with levo-folinate are extensively studied research areas that could combine good therapeutic efficacy with the maintenance of an acceptable quality of life. 34 patients with advanced breast carcinoma were included in the study. Only 4 women had received prior chemotherapy for advanced disease. Treatment plan was: 5-fluorouracil 400 mg/m2 + l-leucovorin 100 mg/m2 days 1-3, cyclophosphamide 600 mg/m2 and mitoxantrone 12-14 mg/m2 on day 3, q28. G-CSF (5 micrograms/kg/d days 7-14) was routinely delivered to the patients with the aim of maintaining dose intensity. 15 patients obtained a response for an overall response rate of 44%. Mean duration was 10.2+ and 11+ months for complete and partial responses respectively. Mean overall survival was 14.4+ months. A high complete response rate was seen in liver metastasis (44%), while lung lesions had a lower probability of response (25%). Toxicity was globally mild with 23% of grade 3 vomiting and 15% of grade 3-4 leukopenia. Two cases of cardiotoxicity were reported. No difference in response rate or toxicity was identified between patients receiving two different mitoxantrone doses (12 or 14 mg/m2). The schedule employed appears to be well tolerated and active in the treatment of advanced breast cancer.(ABSTRACT TRUNCATED AT 250 WORDS)