Safety and efficacy of caspofungin and liposomal amphotericin B, followed by voriconazole in young patients affected by refractory invasive mycosis.
OBJECTIVE
Data on the use of combination of liposomal amphotericin B and caspofungin followed by voriconazole, as maintenance or further rescue treatment, in 10 patients with invasive mycosis are reported.


METHODS
The diagnoses were acute leukemia (7), myelodysplastic syndrome (1) and Hodgkin's lymphoma (1). All patients developed an invasive mycosis (proven, 3; probable, 6; and possible, 1) refractory to first-line antifungal treatment (liposomal amphotericin B in all patients except one who received fluconazole).


RESULTS
Rescue therapy with a combination of caspofungin and liposomal amphotericin B was well tolerated, hypokalemia, and thrombophlebitis being the most common side-effects. Combination therapy was administered for a median of 17 d, range 6-40. Among the nine patients with proven or probable mycosis, one was not evaluated because of early death caused by massive hemoptysis whilst in the remaining eight patients, the response was classified as complete, stable and failure in four, three, and one patients, respectively. Complete response was also observed in patient with possible mycosis. Eight of nine patients received voriconazole for a median of 75 d, range 42-194. Voriconazole was well tolerated although some drug interactions were observed during treatment with methotrexate and digoxin. After a median follow-up of 125 d, nine of 10 patients are alive. Overall, a favorable response to antifungal treatment (including the case of possible mycosis) was obtained in eight of 10 patients.


CONCLUSIONS
These data suggest that medical antifungal treatment may be intensified in severely ill patients without significantly compromising patient safety. The combination of synergistic antifungal drugs as well as their sequential use warrants further investigation by a larger randomized controlled study.
Cesaro
Simone
S
Clinic of Pediatric Hematology Oncology, Department of Pediatrics, Padova, Italy. simone.cesaro@unipd.it
Toffolutti
Tiziana
T
Messina
Chiara
C
Calore
Elisabetta
E
Alaggio
Rita
R
Cusinato
Riccardo
R
Pillon
Marta
M
Zanesco
Luigi
L
D000293:Adolescent; D000328:Adult; D000666:Amphotericin B / Q000008:administration & dosage* / Q000009:adverse effects; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001228:Aspergillosis / Q000188:drug therapy; D001231:Aspergillus flavus; D001232:Aspergillus fumigatus; D000077336:Caspofungin; D002648:Child; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D054714:Echinocandins; D005260:Female; D005847:Geotrichosis / Q000188:drug therapy; D006689:Hodgkin Disease / Q000150:complications; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000150:complications; D055666:Lipopeptides; D008081:Liposomes / Q000008:administration & dosage; D008297:Male; D009181:Mycoses / Q000188:drug therapy* / Q000209:etiology; D009190:Myelodysplastic Syndromes / Q000150:complications; D010455:Peptides / Q000008:administration & dosage* / Q000009:adverse effects; D010456:Peptides, Cyclic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D015996:Survival Rate; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage* / Q000009:adverse effects; D065819:Voriconazole
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D008081:Liposomes; D010455:Peptides; D010456:Peptides, Cyclic; D011743:Pyrimidines; D014230:Triazoles; D000666:Amphotericin B; D000077336:Caspofungin; D065819:Voriconazole