title: 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.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medical Oncology, Radboud University Nijmegen Medical Centre, the Netherlands. J.Timmer@onco.umcn.nl
authors.forename: Johanna N
authors.initials: JN
authors.lastname: Timmer-Bonte
authors.forename: Theo M
authors.initials: TM
authors.lastname: de Boo
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Smit
authors.forename: Bonne
authors.initials: B
authors.lastname: Biesma
authors.forename: Frank A
authors.initials: FA
authors.lastname: Wilschut
authors.forename: Samia A
authors.initials: SA
authors.lastname: Cheragwandi
authors.forename: Arien
authors.initials: A
authors.lastname: Termeer
authors.forename: Cornelis A
authors.initials: CA
authors.lastname: Hensing
authors.forename: Janine
authors.initials: J
authors.lastname: Akkermans
authors.forename: Eddy M
authors.initials: EM
authors.lastname: Adang
authors.forename: Geeben P
authors.initials: GP
authors.lastname: Bootsma
authors.forename: Vivianne C
authors.initials: VC
authors.lastname: Tjan-Heijnen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000890:Anti-Infective Agents / Q000627:therapeutic use; D019072:Antibiotic Prophylaxis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D018288:Carcinoma, Small Cell / Q000150:complications / Q000188:drug therapy*; D002939:Ciprofloxacin / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005334:Fever / Q000139:chemically induced / Q000517:prevention & control; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced* / Q000517:prevention & control*; D012307:Risk Factors; D015575:Roxithromycin / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000890:Anti-Infective Agents; D016179:Granulocyte Colony-Stimulating Factor; D015575:Roxithromycin; D002939:Ciprofloxacin; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide