Phase I/II study with a weekly 24-hour infusion of 5-fluorouracil plus high-dose folinic acid (HD-FU/FA) in intensively pretreated patients with metastatic breast cancer

Summary Background: In metastatic breast cancer patients who have had prior exposure to anthracycline s, single agents induce less than 15% and combination chemotherapy less than 20%-30% of objective responses. Therefore more active and tolerable salvage regimens are needed. Patients and methods: Forty-three patients with advanced breast cancer pretreated with 1-5 (median 2) different chemotherapy regimens were entered into this phase I/H trial. Treatment consisted of folinic acid (FA) (500 mg/m2, i.v., 2-hour infusion) followed by a 24-hour infusion of 5-fluorouracil (FU) which was escalated from 1.5 g/m2 (dose level (dl 1)), to 1.8 g/m2 (dl 2) to 2.1 g/m2 (dl 3). Therapy was given as outpatient treament once weekly times 6 followed by a 2-week rest. Results: FID-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 (gastrointestinal toxicities, hand-foot-syndrome) at dl 3. The response rate for all 32 of the patients treated at dl 3 was 41% (13/32). In the 24 patients 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/FA is a safe outpatient treatment with substantial activity in intensively pretreated breast cancer patients.