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


OBJECTIVE
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.


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 Unpublished trials from conference proceedings and contact to industry.


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


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


RESULTS
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).


CONCLUSIONS
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.
Johansen
H K
HK
The Nordic Cochrane Centre, Rigshospitalet, Dept. 7112, Blegdamsvej 9, DK-2100 Copenhagen O, Denmark. hkj@cochrane.dk
Gotzsche
P C
PC
D000666:Amphotericin B / Q000737:chemistry / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000737:chemistry / Q000627:therapeutic use*; D002626:Chemistry, Pharmaceutical; D006801:Humans; D009369:Neoplasms / Q000150:complications*; D009503:Neutropenia / Q000150:complications / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic
D000935:Antifungal Agents; C068538:liposomal amphotericin B; D000666:Amphotericin B