Amphotericin B lipid soluble formulations versus amphotericin B in cancer patients with neutropenia Stable (no update expected for reasons given in 'What's new')

Abstract

Abstract 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.

Author(s)

Helle Krogh Johansen, Peter C Gøtzsche

Abstract

Plain language summary

Prevention of fungal infections in patients with cancer with amphotericin B

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. The review found that lipid formulations of amphotericin B had fewer adverse effects (less nephrotoxicity and fewer dropouts) than conventional amphotericin B. However, it is not clear whether there are any advantages of these formulations if conventional amphotericin B is administered under optimal circumstances.

Author(s)

Helle Krogh Johansen, Peter C Gøtzsche

Reviewer's Conclusions

Authors' conclusions

Implications for practice

Some lipid soluble formulations of amphotericin B may be better drugs than conventional amphotericin B but their high cost prohibits routine use in most settings. Furthermore, it is not clear whether there are any advantages of these formulations if conventional amphotericin B is administered under optimal circumstances.

Implications for research

There is a need for large trials comparing lipid 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.

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