Amphotericin B lipid soluble formulations vs amphotericin B in cancer patients with neutropenia

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.

To compare the effect and adverse effects of AmBisome and other lipid soluble formulations of amphotericin B with conventional amphotericin B in cancer patients with neutropenia.

MEDLINE and Cochrane Library. Unpublished trials from conference proceedings and contact to industry.

Randomised trials comparing lipid soluble formulations of amphotericin B with conventional amphotericin B.

Data on mortality, invasive fungal infection, nephrotoxicity, serum creatinine and dropouts were extracted by both authors independently.

AmBisome vs conventional amphotericin B (3 trials, 1149 patients): AmBisome tended to be more effective than conventional amphotericin B for invasive fungal infection (relative risk 0.63, 95% confidence interval 0.39 to 1.01, P=0.053) whereas there was no significant difference in mortality (relative risk 0.74, 95% CI 0.52 to 1.07). AmBisome decreased significantly the incidence of nephrotoxicity, defined as a 100% increase in serum creatinine (relative risk 0.51, 95% CI 0.40 to 0.64). Fewer patients dropped out on AmBisome but the difference was not significant (relative risk 0.78, 95% CI 0.56 to 1. 08). Amphotericin B in Intralipid vs conventional amphotericin B (4 trials, 145 patients): There were no significant differences in clinical effect whereas the patients treated with the lipid soluble formulation experienced significantly less nephrotoxicity (relative risk 0.34, 95% CI 0.15 to 0.75) and smaller increases in serum creatinine (weighted mean difference 32 micromol/l, 95% CI 21 to 43 micromol/l). Amphotericin B colloidal dispersion (ABCD) vs conventional amphotericin B (1 trial, 213 patients): There was lower nephrotoxicity with ABCD (relative risk 0.38, 95% CI 0.25 to 0.59).

AmBisome is a better drug than conventional amphotericin B but its high cost prohibits routine use in most settings. Furthermore, the advantages of AmBisome may be smaller than indicated in our review if conventional amphotericin B is administered under optimal circumstances. It is not clear whether other lipid formulations of amphotericin B could offer a worthwhile advantage compared to conventional amphotericin B.