title: Amphotericin B lipid soluble formulations versus amphotericin B in cancer patients with neutropenia.
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.
  
  
  OBJECTIVE
  To compare the benefits and harms of lipid soluble formulations of amphotericin B with conventional amphotericin B in cancer patients with neutropenia.
  
  
  METHODS
  We searched PubMed from 1966 to 7 July 2014 and the reference lists of identified articles.
  
  
  METHODS
  Randomised clinical trials comparing lipid soluble formulations of amphotericin B with conventional amphotericin B.
  
  
  METHODS
  The two review authors independently assessed trial eligibility and risk of bias and abstracted data.
  
  
  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.
  
  
  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.
authors.affiliation: The Nordic Cochrane Centre, Rigshospitalet, Blegdamsvej 9, 3343, Copenhagen, Denmark, DK 2100.
authors.forename: Helle Krogh
authors.initials: HK
authors.lastname: Johansen
authors.forename: Peter C
authors.initials: PC
authors.lastname: Gøtzsche
mesh_terms: 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* / Q000401:mortality; D009503:Neutropenia / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D016032:Randomized Controlled Trials as Topic
chemical_list: D000935:Antifungal Agents; C068538:liposomal amphotericin B; D000666:Amphotericin B