Mitoxantrone, fluorouracil, and L-folinic acid in anthracycline-pretreated metastatic breast cancer patients

In this phase II trial we have evaluatedthe activity and toxicity of a combination regimencontaining mitoxantrone, L-leucovorin, and fluorouracil in patients withadvanced breast cancer pretreated with anthracyclines. Forty-six patientswere included into the study; they received atotal of 227 cycles of chemotherapy. Median agewas 63 years (range 34–78), median performance statuswas 80 (range 60–100). Visceral metastases were presentin 37 patients, 6 patients had bone involvementonly, while 3 patients had soft tissue/lymph nodedisease. Median number of previous chemotherapy regimens foradvanced disease was 2 (range 1–3). Ten patientshad anthracycline primary resistance (progressive disease during treatment).Twenty-three patients received mitoxantrone 12 mg/sqm day 1;fluorouracil 370 mg/sqm and L-folinic acid 100 mg/sqmdays 1–3 administered every three weeks. Another groupof 23 patients were treated with the sameregimen using a prolonged 5FU/L-FA schedule (5 days).Two complete responses and 6 partial responses wererecorded with the 3-day schedule; 7 partial responsesin the 5-day schedule (overall response rate 32.6%,95% C.I. 19–46%). Two partial responses were observedin patients with anthracycline primary resistance. Median responseduration was 9 months (range 3–16). Hematologic toxicitywas mild: grade 3–4 leukopenia was recorded in5 patients, grade 3–4 thrombocytopenia in 3 patients.Grade III–IV stomatitis and diarrhea was recorded in4 and 5 patients respectively (all receiving the5-day 5-FU/L-FA schedule). Cardiac toxicity was observed intwo cases. This regimen proved active in advancedbreast cancer following anthracycline-containing chemotherapy, and the 3-dayschedule could be offered to such patients withacceptable toxicity.