Macrophage Colony‐stimulating Factor Prevents Febrile Neutropenia Induced by Chemotherapy

Abstract

There are very few studies describing the preventive effect of macrophage colony-stimulating factor (M-CSF/CSF-1) on chemotherapy-induced infection. In this study, we evaluated the changes in superoxide anion production by granulocytes before and after chemotherapy in ovarian cancer patients and investigated the preventive effect of M-CSF on chemotherapy-induced febrile neutropenia. Three courses of chemotherapy [paclitaxel 180 mg/m 2 and carboplatin (area under the curve; AUC 5)] were administered to 32 ovarian cancer patients, and seven patients presented febrile neutropenia. In the 25 afebrile patients, the percentage of superoxide anion production by granulocytes was significantly decreased from 86.5 ± ± ± ±7.7 (%) to 75.1 ± ± ± ±8.8 (%) at day 7 and 71.0 ± ± ± ±6.3(%) at day 14 without administration of CSF. However, in the patients who presented febrile neutropenia, it was more severely decreased from 86.8 ± ± ± ±6.8 (%) to 60.0± ± ± ±9.9 (%) at day 7 and 56.8 ± ± ± ±5.0 (%) at day 14 without administration of CSF. When M-CSF was administered to all patients in the next course with the same dose of chemotherapy, the incidence of febrile neutropenia was significantly decreased (P = = = =0.0195), and the duration of fever ( ≥ ≥ ≥ ≥38.0°C) and high serum C-reactive protein (CRP) ( ≥ ≥ ≥ ≥2.0 mg/dl) were also significantly shortened (P = = = =0.0023, P = = = =0.0051). Moreover, in these M-CSF-treated patients, the percentage of superoxide anion production by granulocytes was maintained at the level before chemotherapy. These findings indicate that severe impairment of granulocyte function leads to febrile neutropenia, and that M-CSF reduces the incidence of febrile neutropenia by maintaining or improving granulocyte function.

Macrophage Colony-Stimulating Factor Induces Vascular Endothelial Growth Factor Production in Skeletal Muscle and Promotes Tumor Angiogenesis

“…M-CSF stimulates the survival, proliferation, and differentiation of cells of the mononuclear phagocyte lineage (3). M-CSF reduced the incidence and duration of febrile neutropenia in acute myeloid leukemia patients and ovarian cancer patients during chemotherapy (1,4) and improved the long term prognosis of ovarian cancer patients with no residual tumors (5). Furthermore, M-CSF was reported to have an antitumor effect (2,6,7).…”

Macrophage Colony‐stimulating Factor (M‐CSF) Prevents Infectious Death Induced by Chemotherapy in Mice, While Granulocyte‐CSF Does Not

“…M-CSF significantly increased the granulocyte counts, but the degree of increase was smaller than that for G-CSF in this animal model and in a clinical study in humans. 14,[18][19][20][21] In the M-G group in the present study, improvement in the platelet counts was significantly delayed compared with that in the M group, suggesting that G-CSF delayed improvement in the platelet counts. Long-term use of G-CSF may induce hematopoietic immature progenitor cells to myeloid-committed progenitor cells, resulting in the delayed growth of megakaryocyte progenitors or platelets.…”

“…[9][10][11][12][13] Macrophage colony-stimulating factor (M-CSF/CSF-1) has also been reported to shorten the duration of neutropenia and prevent the onset of infection, although this agent slowly improves the hematopoietic cell system, including granulocyte and platelet counts impaired by chemotherapy. [14][15][16][17][18][19][20][21] A clinically important goal is not to increase the neutrophil counts in patients after chemotherapy, but to prevent the onset of infection in these patients by administering CSF preparations. From the viewpoint of infectious disease prevention, granulocyte function is one of the most important factors, and suppression of this function may lead to serious infection.…”

Mirimostim (macrophage colony‐stimulating factor; M‐CSF) improves chemotherapy‐induced impaired natural killer cell activity, Th1/Th2 balance, and granulocyte function

“…14,22) Furthermore, Nemunaitis et al reported that M-CSF improved the mortality of bone marrow transplant patients who develop invasive fungal infection. 23) Recently, Mizutani et al reported that administration of M-CSF can improve the long-term prognosis of ovarian cancer patients with no residual tumor.…”

“…Recent studies have shown that M-CSF markedly improves chemotherapy-induced impairment of granulocyte functions, 12,15,22) suggesting that improvement of the granulocyte functions leads to the improvement of the immunological functions. Our findings in this study also confirmed that M-CSF improves chemotherapy-induced impairment of granulocyte functions.…”