ACCELERATED CHEMOTHERAPY WITH HIGH-DOSE EPIRUBICIN AND CYCLOPHOSPHAMIDE PLUS R-MET-HUG-CSF IN LOCALLY ADVANCED AND METASTATIC BREAST-CANCER

Background: This study evaluated the toxicity of high-dose epirubicin and cyclophosphamide plus r-met-HUG-CSF (G-CSF) given every 2 weeks an d compared the dose-intensity achieved with this schedule with that ob tained in a previous study we conducted in which the same regimen was given every 3 weeks without G-SCF (EC 21). The secondary objective was to explore the activity of this regimen. Patients and methods: Betwee n December 1991 and March 1994, 41 patients (pts), 19 with locally adv anced breast cancer (LABC) and 22 with metastatic breast cancer (MBC), were given high-dose epirubicin (Hd-Epi) (120 mg/m(2)) and cyclophosp hamide (CTX) (600 mg/m(2)) on day 1 every 14 days (EC 14) plus granulo cyte colony-stimulating factor (G-CSF) (5 mcg/kg/d s.c. on days 2-12). A total of 8 cycles in LABC pts (4 pre- and post-surgery), and 6-8 cy cles in MBC pts were administered. The results were compared with thos e obtained in the previous study. Results: The incidence of WHO grade 3-4 neutropenia was significantly reduced in the EC 14 + G-CSF regimen (25.2% vs. 46.8% in 214 and 250 evaluable cycles, respectively, p < 0 .0001), as well as the incidence of neutropenic fever (7% vs. 3%, p = 0.05). Grade 3-4 anemia (36.6% vs. 8% pts, p = 0.001) and grade 3-4 th rombocytopenia (17.1% vs. 0 pts, p = 0.002), were significantly more f requent in EC 14 +G-CSF. No significant differences in the other side effects were found. A total of 17 of 207 of the cycles (8.2%) were del ayed in the EC 14 + G-CSF vs. 58/271 (21.4%) in the EC 21 (p < 0.0001) . The main reasons for these treatment delays were neutropenia (1% vs. 15%), anemia (3% vs. 0) and thrombocytopenia (1% vs. 0). As a result of treatment acceleration and differences in dose delays, the patients on EC 14 + G-CSF received a higher dose-intensity (Epi 58.51 mg/m(2)/ wk vs. 36.8 mg/ m(2)/wk; CTX 292.52 mg/m(2)/wk vs. 182.9 mg/m(2)/wk). A complete response at surgery was obtained in 9/19 (47.4%) LABC pts. An objective CR was obtained in 11/22 MBC pts (50%) and a partial resp onse in 8/22 (36.4%), yielding an overall response rate of 86.4%. Conc lusions: Hd-Epi + CTX is very active against both LABC and MBC. The ad ministration of G-CSF allows dose intensification of both drugs (a 59. 5% increase of the actual dose intensity) with acceptable clinical tol erance (a lower incidence of neutropenia but a higher incidence of ane mia and thrombocytopenia). Only a specifically designed phase m trial will lead to definitive conclusions regarding the greater antitumor ac tivity of accelerated CSF-including regimens as compared to standard c hemotherapy for advanced breast cancer.