Low-dose amphotericin B lipid complex vs. conventional amphotericin B for empirical antifungal therapy of neutropenic fever in patients with hematologic malignancies--a randomized, controlled trial.

Abstract

BACKGROUND:

Conventional amphotericin B (c-AmB) remains the empirical antifungal treatment of choice for neutropenic patients with persistent fever of unknown origin (FUO). Unfortunately, empirical treatment with c-AmB is hampered by its safety profile, with frequent infusion-related adverse events (IRAEs) and renal toxicity. Amphotericin B lipid complex (ABLC) has been investigated for this indication due to its low toxicity profile. The recommended dose of ABLC is 5 mg/kg/d, which is five to seven times higher than the recommended dose of c-AmB.

METHODS:

This randomized, controlled trial includes 105 adult patients with hematologic malignancies and with FUO after receiving chemotherapy or autologous stem cell transplantation. Patients were randomly allocated to receive ABLC at 1 mg/kg/d or c-AmB at 0.6 mg/kg/d for empirical antifungal therapy.

RESULTS:

The incidence of renal toxicity was significantly lower in the ABLC group, compared with c-AmB group: 8% vs. 32%, respectively (P = 0.003). The rates of IRAEs were similar in both groups (73% for ABLC vs. 77% for c-AmB). The overall response rate was 72% for ABLC compared with 48% for c-AmB (P = 0.018). This difference was mainly due to the significantly higher renal toxicity in the c-AmB group. The number of emergent fungal infections and overall mortality were similar in both groups.

CONCLUSIONS:

This randomized trial suggests that ABLC at 1 mg/kg/d produces less nephrotoxicity than c-AmB, without differences in the incidence of IRAEs and with similar efficacy.

• Authors: Maricel Subirà, Rodrigo Martino, Lucia Gómez, Josep María Martí, Cristina Estany, Jorge Sierra
• Journal: European journal of haematology (Eur J Haematol) Vol. 72 Issue 5 Pg. 342-7 (May 2004) ISSN: 0902-4441 [Print] England
• PMID: 15059069 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright Blackwell Munksgaard 2004.

Chemical References

• Antifungal Agents
• Drug Combinations
• Phosphatidylcholines
• Phosphatidylglycerols
• liposomal amphotericin B
• Amphotericin B

Topics

• Adult
• Amphotericin B (administration & dosage, adverse effects, therapeutic use)
• Antifungal Agents (administration & dosage, adverse effects, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Chemical and Drug Induced Liver Injury (etiology)
• Combined Modality Therapy
• Drug Combinations
• Female
• Fever of Unknown Origin (etiology)
• Hematologic Neoplasms (complications, drug therapy, therapy)
• Humans
• Hypokalemia (chemically induced)
• Immunocompromised Host
• Incidence
• Kidney Diseases (chemically induced, prevention & control)
• Male
• Middle Aged
• Mycoses (drug therapy, etiology)
• Neutropenia (chemically induced, etiology)
• Peripheral Blood Stem Cell Transplantation (adverse effects)
• Phosphatidylcholines (administration & dosage, adverse effects, therapeutic use)
• Phosphatidylglycerols (administration & dosage, adverse effects, therapeutic use)
• Treatment Outcome