Subcutaneous versus intravenous granulocyte colony stimulating factor for the treatment of neutropenia in hospitalized hemato‐oncological patients: Randomized controlled trial

Abstract

Intravenous (IV) granulocyte colony stimulating factor (G-CSF) might be safer and more convenient than subcutaneous (SC) administration to hospitalized hemato-oncological patients receiving chemotherapy. To compare IV vs. SC G-CSF administration, we conducted a randomized, open-label trial. We included inpatients receiving chemotherapy for acute myeloid leukemia, acute lymphoblastic leukemia, lymphoma or multiple myeloma, and allogeneic or autologous hematopoietic cell transplantation (HCT). Patients were randomized to 5 mcg/kg single daily dose of IV bolus versus SC filgrastim given for its clinical indications. Patients were crossed-over to the alternate study arm on the subsequent chemotherapy course. The primary outcomes were time from initiation of filgrastim to recovery of stable neutrophil count of >500 cells/mL and a composite clinical outcome of infection or death assessed for the first course post-randomization. The study was stopped on the second interim analysis. Of 120 patients randomized, 118 were evaluated in the first treatment course. The mean time to neutropenia resolution was longer with IV G-CSF [7.9 days, 95% confidence interval (CI) 6.6-9.1] compared with SC G-CSF (5.4 days, 95% CI 4.6-6.2), log-rank P 5 0.001. Longer neutropenia duration was observed in all patient subgroups, except for patients undergoing autologous HCT. There was no significant difference between groups in the occurrence of infection or death, but more deaths were observed with IV (4/57, 7%) versus SC (1/61, 1.6%) G-CSF administration, P 5 0.196. Similar results were observed when all 158 courses following cross-over were analyzed. Patients reported similar pain and satisfaction scores in both groups. Bolus IV administration of G-CSF results in longer neutropenia duration than SC administration, with no difference in clinical or quality-of-life measures.

The optimal choice of medication administration route regarding intravenous, intramuscular, and subcutaneous injection

“…Paul et al conducted a randomized, open-label trial to compare IV versus SC G-CSF administration to hospitalized hemato-on-cological patients receiving chemotherapy. 32 The mean time to neutropenia resolution was longer with IV G-CSF compared with SC G-CSF (7.9 days versus 5.4 days, P =0.001), indicating that bolus IV G-CSF could result in longer neutropenia duration than SC administration. 32 Eguchi et al evaluated the efficacy and toxicity of recombinant human G-CSF given subcutaneously in patients with advanced lung cancer undergoing intensive chemotherapy.…”

“… 32 The mean time to neutropenia resolution was longer with IV G-CSF compared with SC G-CSF (7.9 days versus 5.4 days, P =0.001), indicating that bolus IV G-CSF could result in longer neutropenia duration than SC administration. 32 Eguchi et al evaluated the efficacy and toxicity of recombinant human G-CSF given subcutaneously in patients with advanced lung cancer undergoing intensive chemotherapy. When G-CSF is given subcutaneously, the dose required for a comparable effect in alleviating neutropenia is 50% of that required when it is given intravenously.…”

G-CSF and GM-CSF in Neutropenia

“…Both drugs may be given subcutaneously or intravenously, although randomized clinical trials demonstrate greater efficacy (i.e., decreased duration of neutropenia) without a difference in toxicity for the subcutaneous route(13). For chemotherapy-induced neutropenia, G-CSF is administered until there is >1000 neutrophils/µl.…”

Association between neutropenia and IgG antineutrophil antibodies in a case of CD40LG deficiency due to two novel mutations

“…Antinuclear antibodies (ANA) were not detected. He received subcutaneous granulocyte‐colony stimulating factor (G‐CSF), according to recommended dosage (5 μg/kg/day = 50 μg Neupogen ® /day), for seven consecutive days, without effect on his neutrophil levels but for a marked increase in his eosinophil counts: 2.2 × 10 9 /L (age‐adjusted range: <0.05 × 10 9 /L). A bone marrow biopsy showed lively erythropoiesis, normal thrombocytopoiesis, inhibited neutropoiesis, normal eosinophilopoiesis, and no signs of neoplastic hematologic disease.…”