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.
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.
Timmer-Bonte
Johanna N
JN
Department of Medical Oncology, Radboud University Nijmegen Medical Centre, the Netherlands. J.Timmer@onco.umcn.nl
de Boo
Theo M
TM
Smit
Hans J
HJ
Biesma
Bonne
B
Wilschut
Frank A
FA
Cheragwandi
Samia A
SA
Termeer
Arien
A
Hensing
Cornelis A
CA
Akkermans
Janine
J
Adang
Eddy M
EM
Bootsma
Geeben P
GP
Tjan-Heijnen
Vivianne C
VC
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
D000890:Anti-Infective Agents; D016179:Granulocyte Colony-Stimulating Factor; D015575:Roxithromycin; D002939:Ciprofloxacin; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide