Incorporation of Amphotericin B into liposomes reduces the drug's cytotoxicity in immunocompromised cancer patients, but does not diminuish the antifungal activity. Experimental therapy with low dose Ampothericin B of pulmonary fungal infections in 36 immunocompromised patients with thoracic tumors, hospitalised in the Istituto Nazionale Tumori, Milano, is reported. The fungal infections developed after surgery or following chemo-radiotherapy induced neutropenia. Before microbiological response 33 high risk patients had received (as a standard prophylactic antifungal treatment) fluconazole, about 3.5 mg/kg/day iv, but after 7-9 days of therapy symptoms suggesting deep mycosis were detected Another 3 patients not treated with fluconazole showed similar symptoms. Twenty-nine cases had invasive aspergillosis and seven deep candidosis. The infection was revealed by BAL, blood culture, and CT scan of chest. A liposomal formulation (AmBisome) was selected, with a low-dose schedule (in the range 1 to 2.2 mg/kg/day iv for 10 days), in order to avoid as much as possible any adverse events in these critically ill subjects. We obtained fungal sterilization in 10 days versus 20 and more of conventional treatment. No adverse reactions that could be attributed to AmBisome were detected, probably because of the low doses and of the short term treatment. After 5-65 months, 30 patients were alive: no mycotic relapses or reinfections were detected. Six patients died for ARDS and for progression of cancer, but free of fungal infections. In conclusion, in critically ill patients with thoracic malignancies, low-dose liposomal Amphotericin B (AmBisome) resulted in complete eradication of pulmonary Aspergillus and Candida infections and was remarkably well tolerated.
Full conference title:
3rd European Congress of Chemotherapy, May 2000
- ECC 3rd (2000)