1 Department of Immunology and Microbiology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, Københavns Universitet2 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet3 Department of Immunology and Microbiology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, Københavns Universitet4 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet
BACKGROUND: Patients with cancer who are treated with chemotherapy or receive a bone marrow transplant have an increased risk of acquiring fungal infections. Such infections can be life-threatening. Antifungal drugs are therefore often given prophylactically to such patients, or when they have a fever. OBJECTIVES: To compare the benefits and harms of lipid soluble formulations of amphotericin B with conventional amphotericin B in cancer patients with neutropenia. SEARCH METHODS: We searched PubMed from 1966 to 7 July 2014 and the reference lists of identified articles. SELECTION CRITERIA: Randomised clinical trials comparing lipid soluble formulations of amphotericin B with conventional amphotericin B. DATA COLLECTION AND ANALYSIS: The two review authors independently assessed trial eligibility and risk of bias and abstracted data. MAIN RESULTS: We found 13 trials (1960 patients). Lipid-based amphotericin B was not more effective than conventional amphotericin B on mortality (relative risk (RR) 0.5; 95% confidence interval (CI) 0.64 to 1.14) but decreased invasive fungal infection (RR 0.65; 95% CI 0.44 to 0.97), nephrotoxicity defined as a 100% increase in serum creatinine (RR 0.45; 95% CI 0.37 to 0.54), and number of dropouts (RR 0.78; 95% CI 0.62 to 0.97).For the drug used in most patients, AmBisome (4 trials, 1214 patients), there was no significant difference in mortality (RR 0.77; 95% CI 0.54 to 1.10) whereas it tended to be more effective than conventional amphotericin B on invasive fungal infection (RR 0.63; 95% CI 0.39 to 1.01, P value 0.053).AmBisome, amphotericin B in Intralipid (6 trials, 379 patients), amphotericin B colloidal dispersion (ABCD) (2 trials, 262 patients), and amphotericin B lipid complex (ABLC) (1 trial, 105 patients) all decreased the occurrence of nephrotoxicity, but conventional amphotericin B was rarely administered under optimal circumstances. AUTHORS' CONCLUSIONS: It is not clear whether there are any advantages of lipid-based formulations if conventional amphotericin B is administered under optimal circumstances, and their high cost prohibits routine use in most settings. There is a need for large trials comparing lipid-based formulations of amphotericin B with conventional amphotericin B given in the same dose, with routine premedication for prevention of infusion-related toxicity, and with supplementation with fluid, potassium, and magnesium for prevention of nephrotoxicity.
Journal review article
Cochrane Database of Systematic Reviews, 2014, Vol 9, p. 1-30