Efficacy and safety of intravenous voriconazole and intravenous itraconazole for antifungal prophylaxis in patients with acute myelogenous leukemia or high-risk myelodysplastic syndrome.
OBJECTIVE
To compare the efficacy and safety of voriconazole with itraconazole as prophylaxis in leukemia patients.


METHODS
Open-label, randomized study. Patients with acute myelogenous leukemia or high-risk myelodysplastic syndrome undergoing induction chemotherapy or first salvage were eligible. Patients received voriconazole (400 mg intravenous (i.v.) every 12 h for two doses, followed by 300 mg BID) or itraconazole (200 mg i.v. twice daily for 2 days, followed by 200 mg i.v. daily).


RESULTS
A total of 127 patients were enrolled. Four were excluded because they did not receive study drug (n=3) or received two antifungal agents during the first week on study (n =1), leaving 123 patients for analysis. None of the 71 patients receiving voriconazole developed proven or probable invasive fungal infection, compared to two (4%) of the 52 patients receiving itraconazole (P=0.17). Drug discontinuation because of adverse events occurred in 15 patients (21%) receiving voriconazole and six (11%) receiving itraconazole (P=0.23).


CONCLUSIONS
Voriconazole is a good alternative for prophylaxis in patients with leukemia. Elevated baseline bilirubin levels were associated with a higher risk of side effects in patients receiving i.v. voriconazole or i.v. itraconazole. Monitoring of liver function and drug levels should be considered for some patients.
Mattiuzzi
Gloria N
GN
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 428, Houston, TX 77030, USA. gmattiuz@mdanderson.org
Cortes
Jorge
J
Alvarado
Gladys
G
Verstovsek
Srdan
S
Koller
Charles
C
Pierce
Sherry
S
Blamble
Deborah
D
Faderl
Stefan
S
Xiao
Lianchun
L
Hernandez
Mike
M
Kantarjian
Hagop
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001663:Bilirubin / Q000097:blood; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D017964:Itraconazole / Q000009:adverse effects / Q000627:therapeutic use*; D015470:Leukemia, Myeloid, Acute / Q000150:complications / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000209:etiology / Q000517:prevention & control*; D009190:Myelodysplastic Syndromes / Q000150:complications / Q000188:drug therapy; D011446:Prospective Studies; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*; D065819:Voriconazole; D055815:Young Adult
D000935:Antifungal Agents; D000970:Antineoplastic Agents; D011743:Pyrimidines; D014230:Triazoles; D017964:Itraconazole; D065819:Voriconazole; D001663:Bilirubin