Amphotericin B lipid soluble formulations versus amphotericin B in cancer patients with neutropenia
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Amphotericin B lipid soluble formulations versus amphotericin B in cancer patients with neutropenia. / Johansen, Helle Krogh; Gøtzsche, Peter C.
In: Cochrane Database of Systematic Reviews, Vol. 9, CD000969, 2014, p. 1-30.Research output: Contribution to journal › Review › Research › peer-review
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TY - JOUR
T1 - Amphotericin B lipid soluble formulations versus amphotericin B in cancer patients with neutropenia
AU - Johansen, Helle Krogh
AU - Gøtzsche, Peter C
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
U2 - 10.1002/14651858.CD000969.pub2
DO - 10.1002/14651858.CD000969.pub2
M3 - Review
C2 - 25188673
VL - 9
SP - 1
EP - 30
JO - Cochrane Database of Systematic Reviews
JF - Cochrane Database of Systematic Reviews
SN - 1361-6137
M1 - CD000969
ER -
ID: 137816549