Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia.
BACKGROUND
Patients with persistent fever and neutropenia often receive empirical therapy with conventional or liposomal amphotericin B for the prevention and early treatment of invasive fungal infections. Caspofungin, a member of the new echinocandin class of compounds, may be an effective alternative that is better tolerated than amphotericin B.


METHODS
In this randomized, double-blind, multinational trial, we assessed the efficacy and safety of caspofungin as compared with liposomal amphotericin B as empirical antifungal therapy. At study entry, patients were stratified according to risk and according to whether they had previously received antifungal prophylaxis. A successful outcome was defined as the fulfillment of all components of a five-part composite end point.


RESULTS
Efficacy was evaluated in 1095 patients (556 receiving caspofungin and 539 receiving liposomal amphotericin B). After adjustment for strata, the overall success rates were 33.9 percent for caspofungin and 33.7 percent for liposomal amphotericin B (95.2 percent confidence interval for the difference, -5.6 to 6.0 percent), fulfilling statistical criteria for the noninferiority of caspofungin. Among patients with baseline fungal infections, a higher proportion of those treated with caspofungin had a successful outcome (51.9 percent vs. 25.9 percent, P=0.04). The proportion of patients who survived at least seven days after therapy was greater in the caspofungin group (92.6 percent vs. 89.2 percent, P=0.05). Premature study discontinuation occurred less often in the caspofungin group than in the amphotericin B group (10.3 percent vs. 14.5 percent, P=0.03). The rates of breakthrough fungal infections and resolution of fever during neutropenia were similar in the two groups. Fewer patients who received caspofungin sustained a nephrotoxic effect (2.6 percent vs. 11.5 percent, P<0.001), an infusion-related event (35.1 percent vs. 51.6 percent, P<0.001), or a drug-related adverse event or discontinued therapy because of drug-related adverse events.


CONCLUSIONS
Caspofungin is as effective as and generally better tolerated than liposomal amphotericin B when given as empirical antifungal therapy in patients with persistent fever and neutropenia.
National Cancer Institute, National Institutes of Health, Bethesda, Md 20892, USA.
Thomas J
TJ
Walsh
Hedy
H
Teppler
Gerald R
GR
Donowitz
Johan A
JA
Maertens
Lindsey R
LR
Baden
Anna
A
Dmoszynska
Oliver A
OA
Cornely
Michael R
MR
Bourque
Robert J
RJ
Lupinacci
Carole A
CA
Sable
Ben E
BE
dePauw
D000293:Adolescent; D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000077336:Caspofungin; D004311:Double-Blind Method; D054714:Echinocandins; D005260:Female; D005334:Fever / Q000209:etiology; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced; D055666:Lipopeptides; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D009369:Neoplasms / Q000150:complications / Q000401:mortality / Q000628:therapy; D009503:Neutropenia / Q000209:etiology; D010455:Peptides / Q000009:adverse effects / Q000627:therapeutic use*; D010456:Peptides, Cyclic; D015996:Survival Rate; D016896:Treatment Outcome
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D008081:Liposomes; D010455:Peptides; D010456:Peptides, Cyclic; D000666:Amphotericin B; D000077336:Caspofungin