title: Amphotericin B colloidal dispersion (Amphocil) vs fluconazole for the prevention of fungal infections in neutropenic patients: data of a prematurely stopped clinical trial.
abstract: We conducted an open label, randomised clinical trial to compare amphotericin B colloidal dispersion (ABCD, Amphocil) 2 mg/kg/day intravenously with fluconazole 200 mg/day orally, for the prevention of fungal disease in neutropenic patients with haematological malignancies. In the event of unresolved fever after 4 days of empirical antibacterial therapy, patients in both treatment groups were to receive ABCD, 4 mg/kg/day. However, the study had to be stopped in an early phase, due to severe side-effects of ABCD. A total of 24 patients were enrolled, 12 patients were randomly assigned to receive prophylactic ABCD, which was administered for a mean of 13.9 days. Fluconazole prophylaxis was given to 12 patients for a mean of 21.2 days. Therapeutic ABCD, 4 mg/kg, was initiated in four patients because of suspected fungal infection, all of whom had initially received fluconazole. A high rate of infusion-related toxicity of ABCD was observed. Chills occurred in 15/16 ABCD recipients (94%), accompanied by a temperature rise of >/=2 degrees C in 4/16 patients and of >/=1 degrees C but <2 degrees C in 10/16 patients. Other ABCD-related adverse events were hypotension (4/16), nausea with vomiting (5/16), tachycardia (7/16), headache (3/16) and dyspnoea (3/16). For premedication patients received: antihistamines (12/16), hydrocortisone (9/16) and/or morphine (6/16). ABCD was discontinued in 8/16 patients (50%) due to side-effects, which ultimately dictated early termination of the study. We conclude that ABCD is not suitable for antifungal prophylaxis in neutropenic patients due to severe infusion-related side-effects. Subject numbers were too low for conclusions on variables of antifungal efficacy.
authors.affiliation: Department of Haematology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
authors.forename: G J
authors.initials: GJ
authors.lastname: Timmers
authors.forename: S
authors.initials: S
authors.lastname: Zweegman
authors.forename: A M
authors.initials: AM
authors.lastname: Simoons-Smit
authors.forename: A C
authors.initials: AC
authors.lastname: van Loenen
authors.forename: D
authors.initials: D
authors.lastname: Touw
authors.forename: P C
authors.initials: PC
authors.lastname: Huijgens
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000008:administration & dosage / Q000633:toxicity*; D001663:Bilirubin / Q000097:blood; D003257:Consumer Product Safety; D000075202:Contraindications; D005260:Female; D015725:Fluconazole / Q000008:administration & dosage* / Q000633:toxicity; D019337:Hematologic Neoplasms / Q000150:complications* / Q000188:drug therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000627:therapeutic use; D009181:Mycoses / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control*; D009503:Neutropenia / Q000150:complications* / Q000188:drug therapy; D012140:Respiratory Tract Diseases / Q000139:chemically induced; D012768:Shivering; D013534:Survival; D013997:Time Factors; D000637:Transaminases / Q000097:blood
chemical_list: D009020:Morphine; D000666:Amphotericin B; D015725:Fluconazole; D000637:Transaminases; D001663:Bilirubin