Open-label, randomized comparison of itraconazole versus caspofungin for prophylaxis in patients with hematologic malignancies.
Invasive fungal infection remains the most common cause of infectious death in acute leukemia. In this open-label, randomized study, we compared the efficacy and safety of caspofungin with that of intravenous itraconazole for antifungal prophylaxis in patients undergoing induction chemotherapy for acute myelogenous leukemia or myelodysplastic syndrome. Of 200 patients, 192 were evaluable for efficacy (86 for itraconazole, 106 for caspofungin). Duration of prophylaxis (median, 21 days [range, 1 to 38 days]), demographics, and prognostic factors were similar in both groups. Ninety-nine patients completed antifungal prophylaxis without developing fungal infection (44 [51%] with itraconazole, 55 [52%] with caspofungin). Twelve patients developed documented invasive fungal infections, five in the itraconazole group (four with candidemia and one with Aspergillus pneumonia), and seven in the caspofungin group (two with candidemia, two with disseminated trichosporon species, two with Aspergillus pneumonia, and one with disseminated Fusarium spp). Two patients in the itraconazole group and four in the caspofungin group died of fungal infection (P = 0.57). Grade 3 to 4 adverse event rates were comparable between groups; the most common event in both was reversible hyperbilirubinemia. No evidence of cardiovascular toxicity from intravenous itraconazole was noted among patients older than 60. In conclusion, intravenous itraconazole and caspofungin provided similar protection against invasive fungal infection during induction chemotherapy, and both drugs were well tolerated.
Mattiuzzi
Gloria N
GN
Department of Leukemia, Unit 428, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA. gmattiuz@mdanderson.org
Alvarado
Gladys
G
Giles
Francis J
FJ
Ostrosky-Zeichner
Luis
L
Cortes
Jorge
J
O'brien
Susan
S
Verstovsek
Srdan
S
Faderl
Stefan
S
Zhou
Xian
X
Raad
Issam I
II
Bekele
B Nebiyou
BN
Leitz
G J
GJ
Lopez-Roman
Ivonne
I
Estey
Elihu H
EH
D000293:Adolescent; D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000077336:Caspofungin; D054714:Echinocandins; D005260:Female; D019337:Hematologic Neoplasms / Q000401:mortality / Q000517:prevention & control*; D006801:Humans; D017964:Itraconazole / Q000008:administration & dosage / Q000627:therapeutic use*; D055666:Lipopeptides; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000627:therapeutic use*; D012449:Safety; D016896:Treatment Outcome
D000935:Antifungal Agents; D000970:Antineoplastic Agents; D054714:Echinocandins; D055666:Lipopeptides; D010456:Peptides, Cyclic; D017964:Itraconazole; D000077336:Caspofungin