Amphotericin B colloidal dispersion (Amphocil) vs fluconazole for the prevention of fungal infections in neutropenic patients: data of a prematurely stopped clinical trial

We conducted an open label, randomised clinical trial to compare amphoteric in B colloidal dispersion (ABCD, Amphocil) 2 mg/kg/day intravenously with f luconazole 200 mg/day orally, for the prevention of fungal disease in neutr openic patients with haematological malignancies. In the event of unresolve d fever after 4 days of empirical antibacterial therapy, patients in both t reatment groups were to receive ABCD, 4 mg/kg/day, However, the study had t o 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 receiv e prophylactic ABCD, which was administered for a mean of 13.9 days. Flucon azole prophylaxis was given to 12 patients for a mean of 21.2 days. Therape utic ABCD, 4 mg/kg, was initiated in four patients because of suspected fun gal 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 greater than o r equal to 2 degrees C in 4/16 patients and of greater than or equal to 1 d egrees C but <2 degrees C in 10/16 patients. Other ABCD-related adverse eve nts 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), ABC D was discontinued in 8/16 patients (50%) due to side-effects, which ultima tely dictated early termination of the study. We conclude that ABCD is not suitable for antifungal prophylaxis in neutropenic patients due to severe i nfusion-related side-effects. Subject numbers were too low for conclusions on variables of antifungal efficacy.