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Title
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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
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Author
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Institution/Organisation
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European Organisation for Research and Treatment of Cancer-Lung Cancer Group
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Abstract
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| Background: CDE (cyclophosphamide, doxorubicin, etoposide) is one of the standard chemotherapy regimens in the treatment of small-cell lung cancer (SCLC), with myelosuppression as dose-limiting toxicity. In this trial the impact of prophylactic antibiotics on incidence of febrile leucopenia (FL) during chemotherapy for SCLC was evaluated. Patients and methods: Patients with chemo-naive SCLC were randomized to standard-dose CDE (C 1000 mg/m(2) day 1, D 45 mg/m(2) day 1, E 100 mg/m(2) days 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 prophylactic 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 overall 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 less hospitalizations due to FL (31 vs. 17 patients, P = 0.013; 1-sided). However, 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 vs. five (6%) in the placebo arm (P = 0.022; 2-sided). Conclusions: Prophylactic ciprofloxacin plus roxithromycin during CDE chemotherapy reduced the incidence of FL, the number of infections, the use of therapeutic antibiotics and hospitalizations due to FL by approximately 50%, with reduced number of infectious deaths. For patients with similar risk for FL, the prophylactic use of antibiotics should be considered. |
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Language
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English
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Source (journal)
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Annals of oncology / European Society for Medical Oncology. - Amsterdam
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Publication
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Amsterdam
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2001
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ISSN
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0923-7534
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DOI
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10.1023/A:1012545507920
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Volume/pages
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12
:10
(2001)
, p. 1359-1368
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ISI
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000171940400013
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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