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

Citation
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
Citations number
26
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
ANNALS OF ONCOLOGY
ISSN journal
09237534 → ACNP
Volume
12
Issue
10
Year of publication
2001
Pages
1359 - 1368
Database
ISI
SICI code
0923-7534(200110)12:10<1359:ROCFLB>2.0.ZU;2-U
Abstract
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.