An open-label, randomized trial of the effects of macrophage versus granulocyte colony-stimulating factor on natural killer cell activity, lymphokine activated killer cell activity, interleukin-2 production, and leukocyte count in patients after chemotherapy for ovarian cancer

Abstract

An open-label, randomized trial was carried out to determine the effects of human urine macrophage colony-stimulating factor (hM-CSF) and granulocyte colony-stimulating factor (G-CSF) on natural killer (NK) cell activity, lymphokine activated killer (LAK) cell activity, interleukin-2 (IL-2) production, and peripheral white blood cell (WBC) count in patients receiving chemotherapy for ovarian cancer. Twenty patients with ovarian cancer who had received chemotherapy consisting of a combination of carboplatin (280 mg/m 2 intravenously [IV], day 1) and cisplatin (70 mg/m 2 IV, day 2) were randomly divided into two groups. Group A was given hM-CSF 8 × 10 6 U/body per day IV for 5 days from the 14th day after the start of chemotherapy, and group B was given G-CSF 75 μg/body per day subcutaneously for 5 days from the 14th day after the start of chemotherapy. Blood was sampled four times as follows: before chemotherapy; before CSF administration; on the third day of CSF administration; and on the day after completion of CSF administration. The number of peripheral WBCs, NK cell activity, LAK activity, and IL-2 production were determined. The final evaluation was performed in 16 patients (8 patients in each group). In group B, the number of peripheral WBCs was significantly increased to 7763 ± 2477/mm 3 on the third day of G-CSF administration compared with the number before administration of G-CSF (4113 ± 1186/mm 3). There are no significant changes in WBC count in group A. No significant differences in NK cell activity or IL-2 production were observed between groups. In group A, NK cell activity was significantly increased to 34 ± 14% on the third day of hM-CSF administration compared with the activity before administration of hM-CSF (23 ± 15%). In group A, IL-2 production increased to 11.9 ± 6.0 U/mL on the third day of hM-CSF administration compared with 5.9 ± 3.4 U/mL before administration, but the increase in IL-2 production failed to reach statistical significance. In group B, there were no significant changes in NK cell activity or IL-2 production before or after administration of G-CSF. These results suggest that G-CSF is valuable in augmenting WBC counts lowered due to anticancer chemotherapy. The results also suggest that hM-CSF is a valuable cytokine in improving immune function, particularly NK cell activity that has been suppressed by anticancer chemotherapy.