Granulocyte colony-stimulating factor shortens the optimal interval of repetition of chemotherapy with cyclophosphamide in mice.

To examine the effect of human granulocyte colony-stimulating factor (G-CSF) on the hemopoietic response to repeated treatment with the anticancer drug cyclophosphamide (CPA) in mice, we determined the optimal time interval between CPA doses which was required to equalize the recovery of neutrophils in the first and second cycle. G-CSF-treatment significantly shortened the optimal time interval of CPA doses when compared with treatment with the control vehicle. The studies on resistance to a second CPA cycle and hemopoietic parameters indicated that the resistance correlated positively with the granulocyte colony-forming cel (G-CFC) population in marrow, in both control and G-CSF-treated mice. In G-CSF-treated mice, moreover, the resistance correlated positively with the ratio of G-CFC in proliferative state and negatively correlated with the neutrophil levels in peripheral blood. These results suggest that G-CSF shortens the optimal time interval between CPA doses not only by accelerating the recovery of G-CFC but also by affecting the hemopoietic environment.