Treatment of refractory metastatic breast cancer with 5-fluorouracil plus levofolinic acid as continuous venous infusion: A phase II study

Effective palliation of metastatic breast carcinoma (MBC) after the failure of front-line chemotherapy for advanced disease, often based on the use of anthracyclines and taxanes, is quite difficult to achieve due to the devel opment of dominant neoplastic cellular clones highly resistant to further t herapy. Therefore the therapeutic index of second and third line chemothera peutic treatments is usually quite low. Thirty patients with MBC with progr essive disease after anthracycline-based chemotherapy as first line therapy were treated with I-FA 100 mg/m(2)/day and 5U 1000 mglm21day an continuous venous mg:rn infusion for 96 hours every 4 weeks. Most patients (60%) had multiple sites of disease at entry and had visceral lesions as the dominant site of disease Twenty-eight patients were evaluated for objective respons e: two patients had clinically progressive disease before restaging after t he third cycle of chemotherapy. These patients were considered progressive disease since all patients were included in an intent-to-treat analysis. Ni ne patients achieved partial response for an overall response rate of 30% ( intent-to-treat analysis) with a median duration of 9.5+ months (range 4.0/ 14.0 months), and disease stability was obtained in 10 cases (33%) with a m edian duration of 5.5 months (5-11). Progressive disease was recorded in 9 patients. After a median follow-rip of II months, the overall median surviv al time of the whole series of patients was 14.0+ months. Objective respons es were recorded both at visceral and bone sites. Chemotherapeutic treatmen t was generelly quite well tolerated. No toxic deaths were recorded. Among gastrointestinal side-effects grade 3 stomatitis was noted in 30% of patien ts, and grade 3 diarrhea in 10% of cases. Grade 3-4 leukopenia was observed in 23% of patients, but significant episodes of febrile neutropenia were l imited (2 patients). Grade 3 thrombocytopenia was seen only occasionaly in 1 patient. Grade 1 anemia was recorded in 10% of patients. Hand-foot syndro me was noted in 2 patients (7%). Cardiotoxicity was minimal. The combinatio n of 5FU and high-dose I-FA given as 96 hour continuous venous infusion was active, at least in terms of the overall response late, against anthracycl ine refractory metastatic breast carcinoma. These results compare favourabl y with bolus 5FU/FA or other salvage regimens in terms of antineoplastic ac tivity and is well tolerated both subjectively and objectively by most pati ents.