Does granulocyte colony-stimulating factor worsen anemia in early breast cancer patients treated with epirubicin and cyclophosphamide?

Purpose We report on the effects of granulocyte colony-stimulating factor (G-CSF) on hemoglobin (Hb) value in early breast cancer patients receiving high-dose epirubicin and cyclophosphamide (EC) adjuvant treatment. Methods Five hundred and six stage I or stage II female breast cancer patients were treated with E 120 mg/m(2) and C 600 mg/m(2) with or without G-CSF and randomly assigned to receive in a factorial 2 X 2 design: EC; EC + lonidamine; EC + G-CSF; EC + lonidamine + G-CSF. Five consecutive G-CSF schedules tested 100 randomly assigned patients each: (1) 480 jig subcutaneously on days 8 to 14; (2) 480 mu g on days 8, 10, 12, 14; (3) 300 mu g on days 8 to 14; (4) 300 mu g on days 8, 10, 12, and 14; and (5) 300 mu g on days 8 and 12. The mean Hb level of 246 patients receiving EC plus G-CSF was compared with that of 240 patients receiving EC alone. The data presented are derived from an exploratory hypothesis-generating analysis. Results The EC dose intensity did not statistically differ between the G-CSF and the control arm. From the third cycle onward, the mean Hb value resulted significantly lower in G-CSF arm compared with control at each time point of each cycle (P <.0001). No statistically significant difference in the mean Hb level was observed between schedule 5 and control. Of interest, from the second course onward, the mean Hb level tended to be lower in patients receiving seven or four G-CSF injections compared with those patients who received only two injections. Conclusion Our data suggest that a G-CSF dose-related effect may play a role in worsening anemia in patients receiving adjuvant EC.