Prevention of chemotherapy-induced febrile neutropenia (FN) by antibiotics (AB) versus antibiotics plus granulocyte-colony stimulating factor (G-CSF) in small cell lung cancer (SCLC): A randomized phase III study

Abstract

8002 Background: FN is a major complication of chemotherapy in patients (pts) with SCLC. G-CSF is used to prevent FN, but its primary use is only recommended in pts with a considerable (>40%) risk of FN (ASCO guidelines, JCO 2000). AB are also effective in preventing FN, even reduce infection-related mortality and are cost-effective (Tjan-Heijnen, Ann Oncol 2001). In this multicenter randomised phase III trial the role of combined primary prophylaxis with AB plus G-CSF in pts with SCLC at increased risk of FN was determined. Methods: Pts with SCLC-limited disease and performance status (PS) 2–3, or age over 60 years or judged not suitable for concurrent chemo/radiotherapy and pts with SCLC-extensive disease were considered at increased risk of FN. Pts were stratified for age (</≥ 60 years), PS (0–1/2), extend of disease (LD/ED) and line of therapy (1st/2nd) and randomised for primary prophylaxis with AB (ciprofloxacin 500mg + roxithromycin 150mg, bid, days 4–13) alone or in combination with G-CSF (filgrastim 5 μ g/kg/day days 4–13). Chemotherapy consisted of cyclophosphamide 1000mg/m2 day 1, doxorubicin 45mg/m2 day 1 and etoposide 100mg/m2 days 1,2,3, i.v., q 3 weeks, × 5. Primary endpoint: incidence of FN in first cycle, targeted accrual: N=156 pts (78/ arm). Results: See table;171 pts were eligible. Patient characteristics were well balanced. Conclusion: The addition of primary prophylactic G-CSF to prophylactic antibiotics significantly reduced the incidence of chemotherapy-related FN in SCLC patients at increased risk of FN, especially in the first cycle by 50%. Supported by a research grant of Dutch Healthcare Insurance Board. No significant financial relationships to disclose.