Prevention of Chemotherapy-Induced Febrile Neutropenia by Prophylactic Antibiotics Plus or Minus Granulocyte Colony-Stimulating Factor in Small-Cell Lung Cancer: A Dutch Randomized Phase III Study

PURPOSE: Febrile neutropenia (FN) is a major complication of chemotherapy. Antibiotics as well as granulocyte colony-stimulating factor (G-CSF) are effective in preventing FN. This multicenter randomized phase III trial determines whether the addition of G-CSF to antibiotic prophylaxis can further reduce the incidence of FN in patients with small-cell lung cancer (SCLC) at the risk of FN. PATIENTS AND METHODS: Patients (N = 175) were stratified for stage of disease, performance status, age, and prior chemotherapy treatment, and were randomly assigned for treatment with cyclophosphamide, doxorubicin, and etoposide (CDE), followed by prophylactic antibiotics alone (ciprofloxacin and roxithromycin) or by antibiotics in combination with G-CSF on days 4 to 13. RESULTS: In cycle 1, 20 patients (24%) in the antibiotics group developed FN compared with nine patients (10%) in the antibiotics plus G-CSF group (P = .01). In cycles 2 to 5, the incidences of FN were practically the same in both groups (17% v 11%). Only the treatment parameters (odds ratio, 0.33; 95% CI, 0.14 to 0.78) and age (1.067 per year; 95% CI, 1.013 to 1.0124) were related to the probability of FN in cycle 1. CONCLUSION: Primary G-CSF prophylaxis added to primary antibiotic prophylaxis is effective in reducing FN and infections in SCLC patients at the risk of FN with the first cycle of CDE chemotherapy. For patients with similar risk of FN, the combined use of prophylactic antibiotics plus G-CSF can be considered, specifically in the first cycle of chemotherapy.