Tolerance of high doses of amphotericin B by infusion of a liposomal formulation in children with cancer

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Abstract
Conventional amphotericin B (Amph-B) is the drug of choice for treating systemic fungal infections. Recently, a new formulation has become available, encapsulated in liposomes (Amph-lip). This new form of administration was developed in order to lower the acute side effects and to offer the possibility of administering high doses of amphotericin B. Experience with Amph-lip is limited, especially in children. We treated four children with documented systemic fungal infections with Amph-lip and administered it empirically to 12 children. Fifteen of these 16 children were severely granulocytopenic oncologic patients. One 3-month-old baby suffered from systemic candidiasis. Amph-lip was preferred to conventional Amph-B in children with organ dysfunction developing as a consequence of conventional chemotherapy or bone marrow transplantation, after failure of conventional Amph-B to improve a fungal infection, and after adverse drug reactions had occurred. The daily doses of Amph-lip ranged from 1 to 6 mg/kg (median 3 mg/kg), the cumulative doses from 13 to 311 mg/kg (median 75 mg/kg). Acute adverse reactions or organ function abnormalities attributable to Amph-lip did not occur in 402 administrations. Amph-lip has proven to be well tolerated by children in terms of acute toxicity and in the long term. Although large cumulative doses were given, organ function abnormalities attributable to Amph-lip doses were not detected in any of ten long-term survivors over a median observation time of 36 months (range 30–44 months). Amph-lip appears to be a promising alternative antifungal treatment, especially for patients with impaired organ function, when high doses of amphotericin B are necessary.