Perioperative treatment with Filgrastim stimulates granulocyte function and reduces infectious complications after esophagectomy

Abstract

We investigated the effects of recombinant G-CSF (Filgrastim) on the function of neutrophils and the rate of infectious complications in an open-label, nonrandomized study of patients with esophageal cancer undergoing esophagectomy. In this single-center phase-II trial 20 sequential patients (19 evaluable) received Filgrastim at standard doses (300 microg or 480 microg) subcutaneously for 2 days prior to and up to 7 days after surgery. The phagocytotic activity of neutrophils and the oxidative burst in the study group and in an experimental control group (n=27) were measured on days -2, 2, and 10. Neutrophil function was enhanced in the Filgrastim-treated group by factor 1.2 for phagocytosis (p=0.016) and 1.4 for oxidative burst (p)=0.154). Leukocyte counts increased from 7.6 x 10(9)/l (day -2) to a maximum of 45 x 10(9)/l on day 6. No infection was reported in the study group (mean age 59.7 years; 13 men, seven women) up to 10 days after surgery. In contrast, 23 patients (29.9%) in a historical control group (mean age 56 years; 67 men, ten women) treated at the same center developed infections within the first 10 days (p = 0.008). In addition, no postoperative deaths occurred in the study group, compared with 9.1% in the group of historical controls. Thus, in this study, administration of Filgrastim stimulated neutrophil function in patients undergoing esophagectomy, and it might be effective in reducing infectious complications related to the surgical procedure.

Granulocyte Colony-Stimulating Factor Improves Deficient In Vitro Neutrophil Transendothelial Migration in Patients with Advanced Liver Disease

“…Although G-CSF is routinely used to accelerate the recovery of neutrophil counts after chemotherapy and as adjuvant therapy in severe infections in neutropenic patients (4,8), its use in nonneutropenic septic patients or as a prophylactic agent against infection remains controversial (14,25,44,48,55). Our findings suggest the attractive hypothesis that G-CSF could increase neutrophil recruitment to the infective focus in cirrhotic patients and become a possible adjuvant nonantibiotic therapy in prophylaxis and treatment of severe bacterial infections in cirrhotic patients with advanced liver disease.…”

Effects of exogenous recombinant human granulocyte colony-stimulating factor (filgrastim, rhG-CSF) on neutrophils of critically ill patients with systemic inflammatory response syndrome depend on endogenous G-CSF plasma concentrations on admission

“…Most common side effects are bone pain and occasionally skin rash, which appear to be dose-dependent (as reviewed by [12]). The application of filgrastim in patients has been reported to be safe in: i) esophagectomy [9]; ii) acute traumatic brain injury or cerebral hemorrhage [13]; iii) pneumonia and either septic shock or severe sepsis who were receiving mechanical ventilation [14]; and iv) intubated medical-surgical ICU patients for prevention of nosocomial infections [15]. Unfortunately, the clinical efficacy could not be shown, convincingly.…”

“…In previous studies with G-CSF in postoperative/posttraumatic patients at risk of sepsis [6,7,8,9], discrepancies were observed concerning the effects of G-CSF on neutrophil functions. These studies lacked control groups [6,7,8,9], and pre-operative application [6,7,8,9] of recombinant human G-CSF (rhG-CSF; filgrastim) had already been performed.…”

“…These studies lacked control groups [6,7,8,9], and pre-operative application [6,7,8,9] of recombinant human G-CSF (rhG-CSF; filgrastim) had already been performed. However, in many clinical situations, such as in polytraumatized patients, prophylactic application of filgrastim will not be feasible.…”

Application of G-CSF in the Nonneutropenic Host

“…Thus, G-CSF might be also indicated in treatment of patients in late sepsis and immune paralysis. As esophagectomy in patients with esophageal carcinoma is associated with substantial infectious complications, we investigated a possible reduction of the number of postoperative infections by G-CSF in these patients [34]. Nineteen patients were perioperatively treated by daily administration of G-CSF beginning 2 days before surgery for 10 days.…”