Maximum Daily Dose of G-CSF is a Critical Factor for Preventing Recurrence of Febrile Neutropenia in Patients with Gynecologic Cancer: A Case-Control Study

Background: To optimize and to identify the use of granulocyte-colony stimulating factor (G-CSF) and identify critical factors for preventing recurrence of febrile neutropenia (FN) in women undergoing chemotherapy for the treatment of gynecologic cancer. Methods The medical records of consecutive patients who underwent chemotherapy for the treatment of gynecologic cancer and experienced FN at least once at Seoul National University Bundang Hospital from 2003 to 2021 were retrospectively reviewed. Student’s t-test, χ 2 -test, and multivariate forward conditional Cox regression analysis were used to identify the optimal usage of G-CSF and the clinico-laboratory factors that can affect the recurrence of FN. Results A total of 157 patients who met the inclusion criteria were included. Of the 157 patients, 49 (31.2%) experienced recurrence of FN. Age≥55 years (p=0.043), previous lines of chemotherapy≤1 (p=0.002), thrombocytopenia (p=0.025), total dose (p=0.003), and maximum daily dose (p=0.009) of G-CSF were significantly associated with recurrence of FN. However, anemia, septic shock at initial FN, concurrent chemoradiation, maximal target of absolute neutrophil count, and total duration of G-CSF administration were not associated with recurrence of FN. Multiple regression analysis showed that age≥55 years (HR, 2.42; 95% CI, 1.14-5.14; p=0.022), previous chemotherapy≤1 (HR, 4.01; 95% CI, 1.40-11.55; p=0.010), and maximum daily dose of G-CSF≤600 µg (HR, 5.18; 95% CI, 1.12-24.02; p=0.036) were independent risk factors for recurrent FN. Multivariate Cox regression analysis showed that a maximum daily dose of G-CSF≤600 µg was the only independent risk factor for short recurrence-free survival of FN (HR, 4.75; 95% CI, 1.15-19.56; p=0.031). There was no difference in the side effects of G-CSF (bone pain, diarrhea, and deep vein thrombosis) and recovery time from recurrence of FN between maximum daily dose of G-CSF≤600 µg and >600 µg. Conclusions Dose-dense administration of G-CSF>600 µg /day could prevent recurrence of FN in women who undergo chemotherapy for the treatment of gynecologic cancer and FN. Old age and FN at early lines of chemotherapy seem to be associated with FN recurrence.