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

Eur J Haematol. 2004 May;72(5):342-7. doi: 10.1111/j.1600-0609.2004.00239.x.

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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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