Reduction of chemotherapy-induced febrile leucopenia by prophylactic use of ciprofloxacin and roxithromycin in small-cell lung cancer patients: An EORTC double-blind placebo-controlled phase III study
Vcg. Tjan-heijnen et al., Reduction of chemotherapy-induced febrile leucopenia by prophylactic use of ciprofloxacin and roxithromycin in small-cell lung cancer patients: An EORTC double-blind placebo-controlled phase III study, ANN ONCOL, 12(10), 2001, pp. 1359-1368
Background: CDE (cyclophosphamide, doxorubicin, etoposide) is one of the st
andard chemotherapy regimens in the treatment of small-cell lung cancer (SC
LC), with myelosuppression as dose-limiting toxicity. In this trial the imp
act of prophylactic antibiotics on incidence of febrile leucopenia (FL) dur
ing chemotherapy for SCLC was evaluated.
Patients and methods: Patients with chemo-naive SCLC were randomized to sta
ndard-dose CDE (C 1000 mg/m(2) day 1, D 45 mg/m(2) day 1, E 100 mg/m(2) day
s 1-3, i.v., q 3 weeks, x5) or to intensified CDE chemotherapy (125% dose,
q 2 weeks, x4, with filgrastim 5 mug/kg/day days 4-13) to assess the impact
on survival (n = 240 patients). Patients were also randomized to prophylac
tic antibiotics (ciprofloxacin 750 mg plus roxithromycin 150 mg, bid, days
4-13) or to placebo in a 2 x 2 factorial design (first 163 patients). This
manuscript focuses on the antibiotics question.
Results: The incidence of FL during the first cycle was 25% of patients in
the placebo and 11% in the antibiotics arm (P = 0.010; 1-sided), with an ov
erall incidence through all cycles of 43% vs. 24% respectively (P = 0.007;
1-sided). There were less Gram-positive (12 vs. 4), Gram-negative (20 vs. 5
) and clinically documented (38 vs. 15) infections in the antibiotics arm.
The use of therapeutic antibiotics was reduced (P = 0.013; 1-sided), with l
ess hospitalizations due to FL (31 vs. 17 patients, P = 0.013; 1-sided). Ho
wever, the overall number of days of hospitalization was not reduced (P = 0
.05; 1-sided). The number of infectious deaths was nil in the antibiotics v
s. five (6%) in the placebo arm (P = 0.022; 2-sided).
Conclusions: Prophylactic ciprofloxacin plus roxithromycin during CDE chemo
therapy reduced the incidence of FL, the number of infections, the use of t
herapeutic antibiotics and hospitalizations due to FL by approximately 50%,
with reduced number of infectious deaths. For patients with similar risk f
or FL, the prophylactic use of antibiotics should be considered.