Novel antifungal agents as salvage therapy for invasive aspergillosis in patients with hematologic malignancies: posaconazole compared with high-dose lipid formulations of amphotericin B alone or in combination with caspofungin

• Published in: Leukemia Vol. 22; no. 3; pp. 496 - 503
• Main Authors: Raad, I I, Hanna, H A, Boktour, M, Jiang, Y, Torres, H A, Afif, C, Kontoyiannis, D P, Hachem, R Y
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-03-2008; Nature Publishing; Nature Publishing Group
• Subjects: Adult; Amphotericin B; Amphotericin B - administration & dosage; Amphotericin B - therapeutic use; Antifungal agents; Antifungal Agents - administration & dosage; Antifungal Agents - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Aspergillosis; Aspergillosis - drug therapy; Aspergillosis - etiology; Biological and medical sciences; Blood cancer; Cancer Research; Caspofungin; Combined Modality Therapy; Confidence intervals; Critical Care Medicine; Drug Combinations; Drug Therapy, Combination; Echinocandins - administration & dosage; Echinocandins - therapeutic use; Female; Fungal infections; Fungemia - drug therapy; Fungicides; Hematologic and hematopoietic diseases; Hematologic Neoplasms - complications; Hematologic Neoplasms - drug therapy; Hematologic Neoplasms - surgery; Hematology; Hematopoietic Stem Cell Transplantation; Hepatotoxicity; Human mycoses; Humans; Infectious diseases; Intensive; Internal Medicine; Itraconazole - administration & dosage; Itraconazole - therapeutic use; Lipids; Lipopeptides; Male; Malignancy; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Miscellaneous mycoses; Multivariate analysis; Mycoses; Neutropenia - chemically induced; Neutropenia - complications; Oncology; original-article; Phosphatidylcholines - administration & dosage; Phosphatidylcholines - therapeutic use; Phosphatidylglycerols - administration & dosage; Phosphatidylglycerols - therapeutic use; Posaconazole; Pyrimidines - administration & dosage; Pyrimidines - therapeutic use; Salvage Therapy; Therapy; Treatment Outcome; Triazoles - administration & dosage; Triazoles - therapeutic use; Voriconazole; posaconazole; invasive aspergillosis; hematologic malignancy; caspofungin; Human; Drug combination; Mycosis; Hematology; Lipids; Malignant hemopathy; Echinocandine derivatives; Infection; Antifungal agent; Amphotericin B; Polyenic compound; Formulation; Aspergillosis; Caspofungin; Triazole derivatives; Salvage treatment; Posaconazole; Comparative study; Cancer; High malignancy
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/sj.leu.2405065

In patients with hematologic malignancy, invasive aspergillosis continues to be associated with high mortality even when treated with conventional antifungal therapy. To investigate novel antifungal agents, we compared 53 patients who received posaconazole salvage therapy to 52 contemporary control patients who received high-dose lipid formulation of amphotericin B (HD-LPD/AMB at ⩾7.5 mg kg
−1
per day) and 38 other control patients who received caspofungin plus HD-LPD/AMB. Patients in the three groups had similar. The overall response rate to salvage therapy was 40% for posaconazole, 8% for HD-LPD/AMB (
P
⩽0.001) and 11% for combination therapy (
P
<0.002). Aspergillosis contributed to the death of 40% of posaconazole group, 65% of the HD-LPD/AMB group and 68% of the combination group (
P
⩽0.008). By multivariate analysis, posaconazole therapy independently improved response (9.5; 95% confidence interval, 2.8–32.5;
P
<0.001). HD-LPD/AMB alone or in combination was associated with a significantly higher rate of nephrotoxicity (
P
⩽0.02) and hepatotoxicity (
P
<0.03). In conclusion, posaconazole salvage therapy demonstrated greater efficacy and safety than HD-LPD/AMB alone or in combination with caspofungin in the salvage therapy of invasive aspergillosis in hematologic malignancy.