OBJECTIVES: We searched The Cochrane Library, MEDLINE, EMBASE, databases of ongoing trials, and conference proceedings of the American Society of Clinical Oncology and the American Society of Hematology (1980 to December 2015). We planned to include both full-text and abstract publications. Two review authors independently screened search results.
SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing prophylaxis with G(
M)-CSF versus
antibiotics for the prevention of
infection in
cancer patients of all ages receiving
chemotherapy. All study arms had to receive identical
chemotherapy regimes and other supportive care. We included full-text, abstracts, and unpublished data if sufficient information on study design, participant characteristics, interventions and outcomes was available. We excluded cross-over trials, quasi-randomised trials and post-hoc retrospective trials.
DATA COLLECTION AND ANALYSIS: Two review authors independently screened the results of the search strategies, extracted data, assessed risk of bias, and analysed data according to standard Cochrane methods. We did final interpretation together with an experienced clinician.
MAIN RESULTS: In this updated review, we included no new randomised controlled trials. We included two trials in the review, one with 40
breast cancer patients receiving high-dose
chemotherapy and
G-CSF compared to
antibiotics, a second one evaluating 155 patients with
small-cell lung cancer receiving
GM-CSF or
antibiotics.We judge the overall risk of bias as high in the
G-CSF trial, as neither patients nor physicians were blinded and not all included patients were analysed as randomised (7 out of 40 patients). We considered the overall risk of bias in the
GM-CSF to be moderate, because of the risk of performance bias (neither patients nor personnel were blinded), but low risk of selection and attrition bias.For the trial comparing
G-CSF to
antibiotics, all cause mortality was not reported. There was no evidence of a difference for
infection-related mortality, with zero events in each arm. Microbiologically or clinically documented
infections, severe
infections, quality of life, and adverse events were not reported. There was no evidence of a difference in frequency of
febrile neutropenia (risk ratio (RR) 1.22; 95% confidence interval (CI) 0.53 to 2.84). The quality of the evidence for the two reported outcomes,
infection-related mortality and frequency of
febrile neutropenia, was very low, due to the low number of patients evaluated (high imprecision) and the high risk of bias.There was no evidence of a difference in terms of median survival time in the trial comparing
GM-CSF and
antibiotics. Two-year survival times were 6% (0 to 12%) in both arms (high imprecision, low quality of evidence). There were four toxic deaths in the
GM-CSF arm and three in the
antibiotics arm (3.8%), without evidence of a difference (RR 1.32; 95% CI 0.30 to 5.69; P = 0.71; low quality of evidence). There were 28% grade III or IV
infections in the
GM-CSF arm and 18% in the
antibiotics arm, without any evidence of a difference (RR 1.55; 95% CI 0.86 to 2.80; P = 0.15, low quality of evidence). There were 5 episodes out of 360 cycles of grade IV
infections in the
GM-CSF arm and 3 episodes out of 334 cycles in the
cotrimoxazole arm (0.8%), with no evidence of a difference (RR 1.55; 95% CI 0.37 to 6.42; P = 0.55; low quality of evidence). There was no significant difference between the two arms for non-haematological toxicities like diarrhoea,
stomatitis,
infections, neurologic, respiratory, or cardiac adverse events. Grade III and IV
thrombopenia occurred significantly more frequently in the
GM-CSF arm (60.8%) compared to the
antibiotics arm (28.9%); (RR 2.10; 95% CI 1.41 to 3.12; P = 0.0002; low quality of evidence). Neither
infection-related mortality, incidence of
febrile neutropenia, nor quality of life were reported in this trial.
AUTHORS' CONCLUSIONS: