EXPERIMENTAL-STUDY ON SAFETY FOR GRANULOPOIESIS IN SIMULTANEOUS THERAPY WITH RECOMBINANT HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR AND CHEMOTHERAPY

Since recombinant human granulocyte colony-stimulating factor (rhG-CSF ) recruits hematopoietic progenitor cells into the cell cycle, the pos sibility remains that simultaneous injection of rhG-CSF and chemothera peutic agents may aggravate the chemotherapy-induced neutropenia by se nsitizing normal progenitor cells to the cytotoxic effects of chemothe rapeutic agents. Therefore, the use of rhG-CSF is usually restricted f rom the day after chemotherapy. In the present study, we investigated whether concurrent treatment with rhG-CSF and chemotherapeutic agents aggravated granulopoietic failure, using murine neutropenic models. Ne utropenia induced by a single injection of cyclophosphamide, mitomycin C, adriamycin, vincristine, combination of mitomycin C + vincristine, or combination of cyclophosphamide + vincristine + adriamycin (CHOP) was not aggravated by simultaneous injection of rhG-CSF (30 mu g/kg, S C). In contrast, a single concurrent injection of rhG-CSF and 5-fluoro uracil aggravated the neutropenia and the decrease in marrow colony-fo rming unit-granulocyte/macrophage counts, but simultaneous and followi ng injections of rhG-CSF enhanced the recovery of neutrophils. Moreove r, neutropenia induced by successive treatment with cisplatin was prev ented by concurrent treatment with rhG-CSF during the period of the ch emotherapy. From these results, concurrent treatment with rhG-CSF and chemotherapeutic agents with the exception of 5-fluorouracil may be fe asible and well-tolerated in clinical use.