Fluconazole prophylaxis of fungal infections in patients with acute leukemia. Results of a randomized placebo-controlled, double-blind, multicenter trial.
OBJECTIVE
To evaluate the efficacy and safety of fluconazole for prevention of fungal infections.


METHODS
A randomized, placebo-controlled, double-blind, multicenter trial.


METHODS
Adults (257) undergoing chemotherapy for acute leukemia.


METHODS
Patients were randomly assigned to receive either fluconazole (400 mg orally once daily or 200 mg intravenously every 12 hours) or placebo. The study drug was started at initiation of chemotherapy and continued until recovery of neutrophil count, development of proven or suspected invasive fungal infection, or the occurrence of a drug-related toxicity.


METHODS
Fungal colonization, proven superficial or invasive fungal infection, empiric antifungal therapy with amphotericin B, drug-related side effects, and mortality.


RESULTS
Fluconazole decreased fungal colonization (83 of 122 [68%] placebo patients compared with 34 of 119 [29%] fluconazole patients colonized at end of prophylaxis, P < 0.001) and proven fungal infections (27 of 132 [21%] placebo patients compared with 11 of 123 [9%] fluconazole patients infected, P = 0.02). Superficial fungal infections occurred in 20 of 132 (15%) placebo patients but in only 7 of 123 (6%) fluconazole patients (P = 0.01), whereas invasive fungal infections developed in 10 of 132 (8%) placebo patients and in 5 of 123 (4%) fluconazole patients (P = 0.3). Fluconazole was especially effective in eliminating colonization and infection by Candida species other than Candida krusei (66 of 122 [64%] placebo patients colonized at end of prophylaxis compared with 11 of 119 [9%] fluconazole patients, P < 0.001; 22 of 132 [17%] placebo patients infected compared with 7 of 123 [6%] fluconazole patients, P = 0.005). Aspergillus infections were infrequent in both fluconazole (3 cases) and placebo groups (3 cases). The use of amphotericin B, the incidence of drug-related side effects, and overall mortality were similar in both study groups.


CONCLUSIONS
Prophylactic fluconazole prevents colonization and superficial infections by Candida species other than Candida krusei in patients undergoing chemotherapy for acute leukemia and is well tolerated. Fluconazole could not be clearly shown to be effective for preventing invasive fungal infections, reducing the use of amphotericin B, or decreasing the number of deaths.
Winston
D J
DJ
Department of Medicine, UCLA Medical Center 90024.
Chandrasekar
P H
PH
Lazarus
H M
HM
Goodman
J L
JL
Silber
J L
JL
Horowitz
H
H
Shadduck
R K
RK
Rosenfeld
C S
CS
Ho
W G
WG
Islam
M Z
MZ
Buell
D N
DN
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004311:Double-Blind Method; D005260:Female; D015725:Fluconazole / Q000009:adverse effects / Q000627:therapeutic use*; D005658:Fungi / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D007938:Leukemia / Q000150:complications*; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000517:prevention & control*; D009503:Neutropenia / Q000150:complications*; D009894:Opportunistic Infections / Q000517:prevention & control*; D011446:Prospective Studies; D016019:Survival Analysis
D015725:Fluconazole