OBJECTIVE: To determine whether the incidence of febrile leucopenia (FL) is reduced in SCLC patients by administering prophylactic antibiotics thereby reducing resource use and costs associated with treatment. METHODS: A cost-effectiveness analysis was conducted alongside a multicenter phase III randomized controlled trial with a 2x2 factorial design. The trial was designed to compare standard dose CDE (cyclophosphamide, doxorubucin and etoposide) versus intensified CDE (125% dose with G-CSF), with or without prophylactic antibiotics. Patients in the verum arm received roxithromycin 150mg and ciprofloxacin 750mg, both given twice daily for 10 days, commencing the day after completing each cycle of chemotherapy. The economic evaluation examines the costs and effects of patients taking antibiotics versus placebo. Results are presented for 33 patients in The Netherlands, representing 20.5% of the total sample (n=161). Resource utilization data were collected during the trial and included hospitalizations, concomitant medications, transfusions and medical procedures. The viewpoint of the health insurance system is taken, using 1998 prices expressed in Dutch guilders (ppp of 2.07NLG/US$). The effectiveness measures include the incidence of febrile leucopenia and the number of infectious deaths. RESULTS: The average cost attributed to patients in the placebo arm was 12,898 NLG compared to 6,999 NLG in the verum arm, yielding a difference of 5,899 NLG (US$ 2850) (95% CI (-) 2081 - 13,897) in favor of administering prophylactic antibiotics. The clinical trial (n=161) demonstrated a 50% decrease in the incidence of FL and an absolute reduction in the risk of infectious death from 6% to 0% in patients taking antibiotics. CONCLUSION: The use of prophylactic antibiotics in small cell lung cancer patients is cost-effective as it reduces the incidence of FL and infectious deaths whilst reducing direct medical costs by 45%. This study was partly sponsored by Bayer BV