Voriconazole versus amphotericin B in cancer patients with neutropenia.
BACKGROUND
Opportunistic fungal infections are a major cause of morbidity and mortality in neutropenic cancer patients and antifungal therapy are used both empirically and therapeutically in these patients.


OBJECTIVE
To compare the benefits and harms of voriconazole with those of amphotericin B and fluconazole when used for prevention or treatment of invasive fungal infections in cancer patients with neutropenia.


METHODS
MEDLINE and the Cochrane Library (May 2005). Letters, abstracts and unpublished trials were accepted. Contact to authors and industry.


METHODS
Randomised trials comparing voriconazole with amphotericin B or fluconazole.


METHODS
Data on mortality, invasive fungal infection, colonisation, use of additional (escape) antifungal therapy and adverse effects leading to discontinuation of therapy were extracted by two authors independently.


RESULTS
Two trials were included. One trial compared voriconazole to liposomal amphotericin B as empirical treatment of fever of unknown origin (suspected fungal infections) in neutropenic cancer patients (849 patients, 58 deaths). The other trial compared voriconazole to amphotericin B deoxycholate in the treatment of confirmed and presumed invasive Aspergillus infections (391 patients, 98 deaths). In the first trial, voriconazole was significantly inferior to liposomal amphotericin B according to the authors' prespecified criteria. More patients died in the voriconazole group and a claimed significant reduction in the number of breakthrough fungal infections disappeared when patients arbitrarily excluded from analysis by the authors were included. In the second trial, the deoxycholate preparation of amphotericin B was used without any indication of the use of premedication and substitution with electrolytes and salt water to avoid handicapping this drug. This choice of comparator resulted in a marked difference in the duration of treatment on trial drugs (77 days with voriconazole versus 10 days with amphotericin B), and precludes meaningful comparisons of the benefits and harms of the two drugs.


CONCLUSIONS
Liposomal amphotericin B is significantly more effective than voriconazole for empirical therapy of neutropenic cancer patients and should be preferred. For treatment of aspergillosis, there are no trials that have compared voriconazole with amphotericin B given under optimal conditions.
Jørgensen
K J
KJ
Nordic Cochrane Centre, Rigshospitalet, Dept 7112, Blegdamsvej 9, Copenhagen, Denmark, DK-2100. kj@cochrane.dk
Gøtzsche
P C
PC
Johansen
H K
HK
D000666:Amphotericin B / Q000009:adverse effects / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy; D015725:Fluconazole / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008081:Liposomes; D009181:Mycoses / Q000188:drug therapy*; D009369:Neoplasms / Q000150:complications*; D009503:Neutropenia / Q000188:drug therapy* / Q000382:microbiology; D009894:Opportunistic Infections / Q000188:drug therapy*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*; D065819:Voriconazole
D000935:Antifungal Agents; D008081:Liposomes; D011743:Pyrimidines; D014230:Triazoles; D000666:Amphotericin B; D015725:Fluconazole; D065819:Voriconazole