The review concluded that fluoroquinolone prophylaxis reduced the risk of febrile episodes in neutropenic outpatients with solid tumors (including lymphomas) and was associated with a statistically non-significant yet clinically important decrease in mortality in all neutropenic patients. The authors' conclusion regarding mortality appeared somewhat over-optimistic given the data presented and should be interpreted with caution.

To evaluate the prophylactic effectiveness of fluoroquinolone in cancer patients with neutropenia.

MEDLINE, EMBASE, The Cochrane Library, Web of Science, IPA and BIOSIS Previews were searched to October 2005. The search was not limited to studies written in English. Search terms were reported. Reference lists of reviews and eligible trials were searched. Studies published only as abstracts were excluded.

Randomised controlled trials (RCTs) that compared prophylactic fluoroquinolone (as a single agent) with placebo in adults (at least 16 years old) who experienced episodes of neutropenia due to cancer chemotherapy and/or haematopoietic stem cell transplantation were eligible. Studies had to report incidence of all-cause mortality and febrile episodes.

Included studies of were of patients with haematological malignancies (in-patients) or solid tumours (outpatients) treated with either levofloxacin norfloxacin, ciprofloxacin, ofloxacin, enoxacin or pefloxacin, normally at the time of chemotherapy initiation (or two to four days following initiation). Some studies used antifungal and/or antiviral prophylactic cointerventions. Mean/median ages ranged from 40 to 57 years (where stated). Neutropenia was defined as an absolute neutrophil count of less than 500/mm³ in all studies except one. Definitions of fever varied.

Two reviewers independently selected studies for inclusion with 100% agreement.

Two reviewers independently assessed study quality using the criteria: allocation concealment; method of randomisation; outcome ascertainment; use of intention-to-treat (ITT) analysis; and losses to follow-up. Disagreements were resolved by consensus.

One reviewer extracted data to enable calculation of relative risks (RR) and 95% confidence intervals (CI). Investigators were contacted for missing data where necessary.

Meta-analyses to calculate pooled relative risks were performed using a random-effects model. Heterogeneity was assessed using the I² statistic. Pre-specified subgroup analyses investigated effects by type of patient (in-patient or outpatient) and type of quinolone (levofloxacin versus other fluoroquinolones).

Eight RCTs (n=2,721, range 18 to 1,565) were included. All studies were double-blind (including outcome assessors). Allocation concealment and the method of randomisation was adequate in five trials. Seven RCTs used an ITT analysis. Four studies reported no losses to follow-up.

There was no statistically significant difference between treatments in terms of all-cause mortality (RR 0.76, 95% CI 0.54 to 1.08, I²=0%; eight RCTs); subgroup analyses yielded similar results.

There was no statistically significant difference in incidence of febrile episodes (RR 0.76, 95% CI 0.55 to 1.03, I²=96%; eight RCTs).

Subgroup analyses suggested significant benefit for outpatient groups who received fluoroquinolone (RR 0.34, 95% CI 0.14 to 0.80; two RCTs).

Fluoroquinolone prophylaxis reduced the risk of febrile episodes in neutropenic outpatients with solid tumors (including lymphomas) and was associated with a statistically non-significant yet clinically important decrease in mortality in all neutropenic patients.

The review addressed a clear question and was supported by appropriate inclusion criteria. Attempts to identify relevant studies in any language were undertaken by searching electronic databases and checking references. Studies published as abstracts were excluded, so some relevant data may have been missed. Suitable methods were employed to reduce risks of reviewer error and bias during study selection and quality assessment; one reviewer extracted data, so there was a risk of error and bias. Study quality was adequately assessed. Most trials appeared to be of good quality. Suitable methods were used to pool data and assess and investigate heterogeneity.

Several aspects of the review were well-conducted, but the authors' conclusion regarding clinically important effects on mortality appeared somewhat over-optimistic considering the lack of statistical significance and should therefore be interpreted with caution.

Practice: The authors stated that in selected adult populations fluoroquinolone prophylaxis could be used with surveillance for the emergence of resistant pathogens.

Research: The authors did not state any specific implications for research (other than further investigation of their conclusions was needed).

Not stated.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.