Efficacy and toxicity of caspofungin in combination with liposomal amphotericin B as primary or salvage treatment of invasive aspergillosis in patients with hematologic malignancies.
BACKGROUND
Caspofungin (CAS) as salvage therapy for refractory invasive aspergillosis (IA) had a response rate of 45% among a heterogeneous group of patients. The use of CAS with other agents is appealing given its unique mechanism of action. Therefore, the authors retrospectively evaluated the efficacy and toxicity of CAS plus liposomal amphotericin B (LipoAMB) in patients with documented (definite or probable) or possible IA.


METHODS
Patients were evaluable for outcome if they received CAS/LipoAMB for at least 7 days. Patients who received CAS and LipoAMB sequentially were excluded. All patients were evaluable for toxicity. Outcome was assessed weekly and at the end of therapy. Stable disease and progression were considered treatment failures.


RESULTS
Forty-eight patients with documented (n=23) or possible (n=25) IA were identified between March 2001 and December 2001. The majority of the patients (65%) received CAS/LipoAMB as salvage therapy for progressive IA despite 7 or more days of previous LipoAMB monotherapy. The overall response rate was 42%. No significant toxic effects were seen. Factors associated with failure at the end of therapy were documented IA (P=0.03), significant steroid use before the study (P=0.02), and duration of combination therapy for less than 14 days (P=0.01). The response rate in patients with progressive documented IA was low (18%).


CONCLUSIONS
The CAS/LipoAMB combination is a promising preemptive therapy for IA and was generally well tolerated. This combination might have limited benefit as salvage therapy for documented IA.
Kontoyiannis
Dimitrios P
DP
Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. dkontoyi@mdanderson.org
Hachem
Ray
R
Lewis
Russell E
RE
Rivero
Gustavo A
GA
Torres
Harrys A
HA
Thornby
John
J
Champlin
Richard
R
Kantarjian
Hagop
H
Bodey
Gerald P
GP
Raad
Issam I
II
D000293:Adolescent; D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy*; D016026:Bone Marrow Transplantation / Q000276:immunology; D000077336:Caspofungin; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D054714:Echinocandins; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D055666:Lipopeptides; D008172:Lung Diseases, Fungal / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000627:therapeutic use*; D010456:Peptides, Cyclic; D012189:Retrospective Studies; D016896:Treatment Outcome
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D010455:Peptides; D010456:Peptides, Cyclic; D000666:Amphotericin B; D000077336:Caspofungin