MITOXANTRONE, LEUCOVORIN AND HIGH-DOSE INFUSIONAL 5-FLUOROURACIL - ANEFFECTIVE AND WELL-TOLERATED REGIMEN FOR THE TREATMENT OF ADVANCED BREAST-CANCER

Mitoxantrone and 5-fluorouracil (5-FU) are active drugs with a favoura ble toxicity profile in advanced breast cancer. The activity of 5-FU c an be enhanced by modulation with leucovorin. Continuous infusion of S -FU yields a superior activity with less toxicity compared with bolus injections. 27 patients with advanced breast cancer, 22 of them pretre ated, received intravenous (iv) mitoxantrone, 14 mg/m2, day 1, iv leuc ovorin, 300 mg, days 1 and 15, and 5-FU, 4 g, 48-h infusion, days 1 an d 2, 15 and 16, once every 28 days (MLF regimen). Leucovorin was admin istered either as a bolus prior to the 5-FU infusion or mixed together with the 5-FU during the first 24 h. There were 12 partial responses, 9 patients had stable disease, and 5 had progressive disease. 1 patie nt was not evaluable because of concomitant irradiation of the target lesion. The overall response rate was 46%; for previously untreated pa tients it was 100% and for pretreated patients it was 33%. Grade 3 nau sea/vomiting was noted in 7 evaluable patients (26%) and grade 4 haema tological toxicity in 1 patient (4%). Only 1 patient had complete alop ecia. The median duration of response was 13 months in untreated, and 12 months in pretreated patients. It was concluded that MLF is an acti ve regimen in advanced breast cancer, even in highly pretreated patien ts, with moderate and manageable toxicity. Assessment in first-line tr eatment appears to be of interest.