PHASE I II STUDY WITH A WEEKLY 24-HOUR INFUSION OF 5-FLUOROURACIL PLUS HIGH-DOSE FOLINIC ACID (HD-FU/FA) IN INTENSIVELY PRETREATED PATIENTSWITH METASTATIC BREAST-CANCER/

Background: In metastatic breast cancer patients who have had prior ex posure to anthracyclines, single agents induce less than 15% and combi nation chemotherapy less than 20%-30% of objective responses. Therefor e more active and tolerable salvage regimens are needed. Patients and methods: Forty-three patients with advanced breast cancer pretreated w ith 1-5 (median 2) different chemotherapy regimens were entered into t his phase I/II trial. Treatment consisted of folinic acid (FA) (500 mg /m(2), i.v., 2-hour infusion) followed by a 24-hour infusion of 5-fluo rouracil (FU) which was escalated from 1.5 g/m(2) (dose level (dl 1)), to 1.8 g/m(2) (dl 2) to 2.1 g/m(2) (dl 3). Therapy was given as outpa tient treament once weekly times 6 followed by a 2-week rest. Results: HD-FU/FA was well tolerated. No dose-limiting toxicity occurred at dl 1 or 2. Only 3/32 (9%) patients had WHO grade 3/4 toxicities (gastroi ntestinal toxicities, hand-foot-syndrome) at dl 3. The response rate f or all 32 of the patients treated at dl 3 was 41% (13/32). In the 24 p atients with anthracycline-refractory disease, a response rate of 41% (10/24) was achieved. The median remission duration was 11 months and the median survival time 19 months. Conclusions: This schedule of FU/F A is a safe outpatient treatment with substantial activity in intensiv ely pretreated breast cancer patients.