Abstract: 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. As we only found two small trials with 195 patients altogether, no conclusion for clinical practice is possible. More trials are necessary to assess the benefits and harms of G(M)-CSF compared to antibiotics for infection prevention in cancer patients receiving chemotherapy.

Plain-language summary: We searched several medical databases and identified two randomised controlled trials (RCT) that met our inclusion criteria; no new trials were identified for this review update. One trial included 40 breast cancer patients receiving high-dose chemotherapy. Eighteen patients received G-CSF and 22 got antibiotics (ciprofloxacin and amphotericin) to prevent infection. Another trial evaluated GM-CSF versus antibiotics in patients with small-cell lung cancer, with 78 patients in the GM-CSF arm and 77 patients in the antibiotics arm. The study that analysed G-CSF versus antibiotics did not report all cause mortality, microbiologically or clinically documented infections, severe infections, quality of life, or adverse events. We found no evidence of a difference between the two prophylactic options for the outcomes of infection-related mortality (no patient died because of infection), or febrile neutropenia. The trial that assessed GM-CSF versus antibiotics did not found any evidence of a difference in all cause mortality, trial mortality, infections, or severe infections. The only difference between the two arms was found for the adverse event thrombocytopenia, favouring patients receiving antibiotics. Quality of life was not reported in this trial. More research is needed to determine the best prevention against infection in cancer patients. The quality of the evidence for infection-related mortality and frequency of febrile neutropenia in the G-CSF trial was very low, because of the small number of patients that were evaluated, and the study design (high risk of bias). The trial that analysed GM-CSF versus antibiotics reported overall survival, toxic deaths, infections, severe infections, and adverse events. Because of the very small number of patients included, we judged that the overall quality for all these outcomes was low. The evidence is current to December 2015.