AN EORTC PILOT-STUDY OF FILGRASTIM (RECOMBINANT HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR) AS SUPPORT TO A HIGH DOSE-INTENSIVE EPIADRIAMYCIN-CYCLOPHOSPHAMIDE REGIMEN IN CHEMOTHERAPY-NAIVE PATIENTS WITH LOCALLY ADVANCED OR METASTATIC BREAST-CANCER

Background: In an attempt to increase chemotherapy dose intensity by s tep-wise reduction of the time interval between treatment cycles, filg rastim was administered to breast cancer patients receiving a three-mo nth combination chemotherapy with epirubicin (E) and cyclophosphamide (C). Patients and methods: Chemotherapy-naive patients with locally ad vanced or metastatic breast cancer received fixed doses of E (120 mg/m (2)) and C (830 mg/m(2)) by 15-min i.v. infusion on day 1 of each cycl e and filgrastim at a dose of 4 mu g/kg once daily by SC injection sta rting 24 hours after chemotherapy. Cohorts of patients were treated in successive schedules, each schedule corresponding to a specified time interval between chemotherapy cycles. The toxicity observed in each s chedule was evaluated before patients were accrued to the next schedul e, which corresponded to a shorter time interval between chemotherapy cycles. Results: The maximum tolerated schedule was E (120 mg/m(2)) pl us C (830 mg/m(2)) given every 14 days with filgrastim support from da y 2 until day 13. On this schedule, 5 of 12 patients experienced dose- intensity-limiting toxicities (DLT) during the 3-month study period. N on-hematological DLT occurred in 2/12 patients (mucositis, skin toxici ty) while 3/12 experienced febrile neutropenia requiring i.v. antibiot ics. AU patients achieved recovery of ANC to > 1:5 x 10(9)/l by the ti me of scheduled retreatment. The combination of filgrastim with this r egimen did not seem to add major toxicities. The efficacy was high, wi th 87% of patients achieving an objective response and; a median respo nse duration of 18 months (range: 4-52 months). Conclusions: Filgrasti m permits at 33% increase in 'EC' dose intensification over that of th e conventional every-3-week administration. Randomized studies should now be initiated to evaluate the merit, if any, of 'accelerated' chemo therapy in advanced breast cancer.