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 possibility remains that simultaneous injection of rhG-CSF and chemotherapeutic agents may aggravate the chemotherapy-induced neutropenia by sensitizing normal progenitor cells to the cytotoxic effects of chemotherapeutic agents. Therefore, the use of rhG-CSF is usually restricted from 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. Neutropenia 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 micrograms/kg, SC). In contrast, a single concurrent injection of rhG-CSF and 5-fluorouracil aggravated the neutropenia and the decrease in marrow colony-forming unit-granulocyte/macrophage counts, but simultaneous and following injections of rhG-CSF enhanced the recovery of neutrophils. Moreover, neutropenia induced by successive treatment with cisplatin was prevented by concurrent treatment with rhG-CSF during the period of the chemotherapy. From these results, concurrent treatment with rhG-CSF and chemotherapeutic agents with the exception of 5-fluorouracil may be feasible and well-tolerated in clinical use.
Kabaya
K
K
Pharmaceutical Research Laboratory, Kirin Brewery Company, Ltd., Gunma, Japan.
Obuchi
M
M
Watanabe
M
M
Kusaka
M
M
Seki
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D004195:Disease Models, Animal; D004357:Drug Synergism; D016179:Granulocyte Colony-Stimulating Factor / Q000633:toxicity*; D006098:Granulocytes / Q000166:cytology* / Q000187:drug effects*; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009503:Neutropenia / Q000139:chemically induced; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000633:toxicity
D000970:Antineoplastic Agents; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor