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

Abstract

Summary: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 у2؇C in 4/16 patients and of у1؇C but Ͻ2؇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. Bone Marrow Transplantation (2000) 25, 879-884.

Adverse effects of antifungal therapies in invasive fungal infections: review and meta-analysis

“…We report infusion-related reactions requiring discontinuation of ABCD at about 4%. This value includes the patient data of a prematurely stopped clinical trial in which prophylactic ABCD, administered at 2 mg/kg/day, was observed to have unacceptably high rates of infusion-related toxicity, despite the use of antihistamine and antipyretic premedications in most patients [29]. Our analysis showed that 0.3% of patients receiving L-AmB required discontinuation of the medication due to nephrotoxicity.…”

Primary prophylaxis of invasive fungal infections in patients with hematologic malignancies. Recommendations of the Infectious Diseases Working Party of the German Society for Haematology and Oncology

“…83 Intravenous Amphotericin B Lipid Complex and Amphotericin B Colloidal Dispersion prophylaxis may be conceivable as well. 84 However, neither approach has been sufficiently evaluated and cannot be recommended at present.…”

AspergillusInfections in Transplant Recipients

“…Liposomal amphotericin B (Ambisome) at a dose of 2 mg/kg thrice weekly was well tolerated in a randomized, placebo-controlled study, although a beneficial effect of prophylaxis against fungal infections could not be shown (143). Severe infusion-related toxicity led to premature discontinuation of the trial that intended to compare the efficacy of amphotericin B colloidal dispersion with that of fluconazole for the prevention of fungal infections in neutropenic patients (313). Given the uncertain benefit, requirement of parenteral administration, and drug expense, it is unlikely that lipid formulations of amphotericin B would have 60 SINGH AND PATERSON CLIN.…”