Mitoxantrone, 5-fluorouracil and low-dose leucovorin in doxorubicin-resistant advanced breast cancer patients: A phase II study

Aim: Twenty-two anthracycline-resistant advanced breast cancer patients wer e entered from June 1995 till November 1997 in a phase II study to assess t he activity and tolerability of second-line chemotherapy consisting of mito xantrone, 5-fluorouracil and low-dose leucovorin. Study design: Patients were eligible if they failed to respond to doxorubic in-containing chemotherapy, given as first-line chemotherapy for metastatic disease. Treatment consisted of mitoxantrone, 12 mg/m(2) iv infusion on da y 1, and leucovorin, 50 mg iv 1 hr before 5-fluorouracil, 350 mg/m2 iv infu sion on days 1-3, every three weeks. Results: Nineteen patients were eligible for response, 2 refused further th erapy after 2 cycles, and 1 was excluded because grade 3 myelotoxicity deve loped during the first cycle. Partial remission of 15 months duration occur red in 1 patient, in 7/19 women disease remained stable with a median durat ion of 11 months (range, 5-24), and 11/19 patients experienced progressive disease. Median time to disease progression was 2 months (range, 0-17), and median survival was 8 months (range, 0-24), Toxicity was generally mild an d acceptable. One patient was excluded because of grade 3 granulocytopenia and thrombocytopenia, and one due to cardiotoxicity assessed by the drop of left ventricular ejection fraction to more than 20% below the initial valu e. Conclusions: In spite of the very low objective response rate, almost one-f ourth of our anthracycline-resistant patients achieved a disease stabilizat ion of 27 weeks duration during mitoxantrone-based second-line chemotherapy . Hence, mitoxantrone in combination with 5-fluorouracil, especially contin uous infusion, should be further Investigated in this setting, particularly if new and expensive drugs, considered the most active, are not readily av ailable.