We assessed the activity and safety of liposomal
nystatin, a broad-spectrum
antifungal agent, for invasive
aspergillosis in patients refractory to or intolerant of
amphotericin B. Thirty-three patients were enrolled, received at least one dose of the study
drug, and were evaluable for safety. Twenty-six patients had confirmed probable or definite
aspergillosis and were fully eligible. Most patients had a
hematological malignancy (53.8%) or
hematopoietic stem cell transplantation (23.0%), were neutropenic (61.5%), and were refractory to previous
amphotericin B (92.3%). The median duration of previous
amphotericin B treatment was 16.5 days (range, 5 to 64 days).
Aspergillosis was definite in 3 cases and probable in 23 cases. Liposomal
nystatin was initiated at a dose of 4 mg/kg of
body weight/day. Twenty-five patients were evaluable for response: a complete response was achieved for one patient, and a partial response was achieved for six. Thus, the overall response rate is 7 of 25 (28%; 95% confidence interval, 12 to 49%). Seventeen (68.0%) of the 25 evaluable patients died during
therapy or within 1 month after the end of
therapy. The primary cause of death was invasive
aspergillosis for nine patients and underlying
malignancy for eight patients. The most frequent side effects included
chills, shivering, and
fever, leading to discontinuation of
therapy for two patients. Grade 1 decline in renal function was seen for 10 (30.3%) patients, and
hypokalemia was seen for 13 (39.4%). We conclude that liposomal
nystatin can be effective for
salvage therapy of invasive
aspergillosis. Infusion-related adverse events have been observed frequently.