Salvage chemotherapy with high-dose leucovorin (LV) and 48-hour continuousinfusion (CI) of 5-fluorouracil (5-FU) in combination with conventional doses of cyclophosphamide (CPM) in patients with metastatic breast cancer (MBC) pretreated with anthracycline and taxanes

The purpose of this study was to evaluate the activity and tolerance of hig h-dose leucovorin (LV) and infusional 5-fluorouracil (5-FU) in combination with conventional doses of cyclophosphamide (CPM) as salvage chemotherapy i n patients with metastatic breast cancer (MBC) pretreated with anthracyclin es and taxanes. 41 patients (median age 59 years) with MBC refractory or re sistant to anthracyclines and taxanes were enrolled. The patients' performa nce status (WHO) was 0 in 10 patients (24%), 1 in 22 (54%), and 2 in 9 (22% ). 30 (73%) patients had received 2 or more prior chemotherapy regimens. Cy clophosphamide (600 mg m(-2)) was given im. bolus on day 1 and LV (500 ring m(-2) d(-1)) as a 2-h infusion followed by 5-FU (1.5 g m(-2) d(-1)) over a 22 h c,i. for 2 consecutive days. Cyclophosphamide was administered every 28 days while 5-FU/LV every 14 days. In an intention-to-treat analysis, com plete response (CR) was achieved in 2 (4.9%) patients and partial response (PR) in 9 (22%) (overall response rate 26.9%; 95% Cl: 13.27-40.39%). Stable disease (SD) and progressive disease (PID) were observed in 9 (22%) and 21 (51%) patients, respectively. The overall response rate was 6% and 40% in patients with primary and secondary resistance to anthracyclines/taxanes. r espectively (P=0.047). The median duration of response and the median time to disease progression was 8 and 9.5 months, respectively. The median overa ll survival was 13 months and the probability for 1-year survival 51%. Grad e 3/4 neutropenia occurred in 9 (22%) patients and 4 (9%) patients develope d grade 3/4 thrombocytopenia. Non-haematological toxicity was mild. There w ere no cases of febrile neutropenia, toxic deaths or treatment-related hosp ital admissions due to toxicity. The combination of high-dose 5-FU/LV with conventional doses of cyclophosphamide is a well tolerated and effective sa lvage regimen in patients with MBC heavily pretreated with both anthracycli nes and taxanes. (C) 2001 Cancer Research Campaign.