Aerosolized liposomal amphotericin B for the prevention of invasive pulmonary aspergillosis during prolonged neutropenia: a randomized, placebo-controlled trial.
BACKGROUND
Invasive pulmonary aspergillosis (IPA) is a significant problem in patients with chemotherapy-induced prolonged neutropenia. Because pulmonary deposition of conidia is the first step in developing IPA, we hypothesized that inhalation of liposomal amphotericin B would prevent IPA.


METHODS
We performed a randomized, placebo-controlled trial of patients with hematologic disease with expected neutropenia for >or=10 days. Patients were randomized to receive liposomal amphotericin B or placebo inhalation twice a week, using an adaptive aerosol delivery system, until neutrophil counts increased to >300 cells/mm3. In subsequent neutropenic episodes, the assigned treatment was restarted. The primary end point was the occurrence of IPA according to European Organization for Research and the Treatment of Cancer-Mycoses Study Group definitions. Kaplan-Meier curves were compared with log-rank tests for intent-to-treat and on-treatment populations.


RESULTS
A total of 271 patients were studied during 407 neutropenic episodes. According to the intent-to-treat analysis, 18 of 132 patients in the placebo group developed IPA versus 6 of 139 patients in the liposomal amphotericin B group (odds ratio, 0.26; 95% confidence interval, 0.09-0.72; P=.005). According to the on-treatment analysis, 13 of 97 patients receiving placebo versus 2 of 91 receiving liposomal amphotericin B developed IPA (odds ratio, 0.14; 95% confidence interval, 0.02-0.66; P=.007). Some adverse effects, but none serious, in the liposomal amphotericin B group were reported, most frequently coughing (16 patients vs. 1 patient; P=.002).


CONCLUSIONS
In high-risk patients, prophylactic inhalation of liposomal amphotericin B significantly reduced the incidence of IPA.
Rijnders
Bart J
BJ
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands. b.rijnders@erasmusmc.nl
Cornelissen
Jan J
JJ
Slobbe
Lennert
L
Becker
Martin J
MJ
Doorduijn
Jeanette K
JK
Hop
Wim C J
WC
Ruijgrok
Elisabeth J
EJ
Löwenberg
Bob
B
Vulto
Arnold
A
Lugtenburg
Pieternella J
PJ
de Marie
Siem
S
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000008:administration & dosage / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001228:Aspergillosis / Q000209:etiology / Q000517:prevention & control*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008172:Lung Diseases, Fungal / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000150:complications*; D016896:Treatment Outcome
D000935:Antifungal Agents; D000666:Amphotericin B