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.
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.
Subirà
Maricel
M
Division of Clinical Hematology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Av. Sant Antoni Ma. Claret 167, 08025 Barcelona, Spain.
Martino
Rodrigo
R
Gómez
Lucia
L
Martí
Josep María
JM
Estany
Cristina
C
Sierra
Jorge
J
D000328:Adult; D000666:Amphotericin B / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D003131:Combined Modality Therapy; D004338:Drug Combinations; D005260:Female; D005335:Fever of Unknown Origin / Q000209:etiology*; D019337:Hematologic Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000628:therapy; D006801:Humans; D007008:Hypokalemia / Q000139:chemically induced; D016867:Immunocompromised Host; D015994:Incidence; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000188:drug therapy* / Q000209:etiology; D009503:Neutropenia / Q000139:chemically induced / Q000209:etiology*; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects; D010713:Phosphatidylcholines / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D010715:Phosphatidylglycerols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
D000935:Antifungal Agents; D004338:Drug Combinations; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; C068538:liposomal amphotericin B; D000666:Amphotericin B