A Multicenter, double-blind trial of a high-dose caspofungin treatment regimen versus a standard caspofungin treatment regimen for adult patients with invasive candidiasis.
BACKGROUND
The standard caspofungin treatment regimen (50 mg/day after a 70-mg dose on day 1) is effective and well tolerated for the treatment of invasive candidiasis, but experience with higher doses of caspofungin is limited. We evaluated the safety and efficacy of caspofungin at 3 times the standard dosing regimen.


METHODS
Patients with proven invasive candidiasis were randomized to receive a standard or high-dose (150 mg/day) caspofungin treatment regimen. Safety was assessed in all patients as treated. Efficacy was assessed as a secondary objective in a full-analysis-set population. A favorable overall response was defined as symptom resolution and microbiological clearance at the end of caspofungin therapy.


RESULTS
A total of 204 patients were included in the safety analysis (104 received the standard regimen, and 100 received the high-dose regimen), and 197 were included in the efficacy analysis (102 and 95 in the standard and high-dose treatment groups, respectively). Patient demographic characteristics, neutropenia status (6.7% and 8.0% had neutropenia, respectively), and Acute Physiology and Chronic Health Evaluation II scores (mean, 16.5 and 17, respectively) were similar between treatment groups. Significant drug-related adverse events occurred in 1.9% of patients receiving the standard regimen and 3.0% of patients receiving the high-dose regimen (difference, 1.1%; 95% confidence interval, -4.1% to 6.8%). The most-common drug-related adverse events in the standard and high-dose treatment groups were phlebitis (3.8% and 2.0%, respectively), increased alkaline phosphatase level (6.9% and 2.0%, respectively), and increased aspartate transaminase level (4.0% and 2.0%, respectively). Overall, 71.6% of patients who received the standard regimen and 77.9% of patients who received the high-dose regimen had favorable overall responses (difference, 6.3%; 95% confidence interval, -5.9% to 18.4%; not statistically significant). Mortality at 8 weeks after therapy was similar between groups.


CONCLUSIONS
Both caspofungin dosing regimens were effective and well tolerated in patients with invasive candidiasis. No safety concerns were found for caspofungin at a dosage of 150 mg/day.
Betts
Robert F
RF
University of Rochester, Rochester, New York, USA.
Nucci
Marcio
M
Talwar
Deepak
D
Gareca
Marcelo
M
Queiroz-Telles
Flavio
F
Bedimo
Roger J
RJ
Herbrecht
Raoul
R
Ruiz-Palacios
Guillermo
G
Young
Jo-Anne H
JA
Baddley
John W
JW
Strohmaier
Kim M
KM
Tucker
Kimberly A
KA
Taylor
Arlene F
AF
Kartsonis
Nicholas A
NA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000097:blood; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D002177:Candidiasis / Q000188:drug therapy*; D000077336:Caspofungin; D004311:Double-Blind Method; D054714:Echinocandins / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D055666:Lipopeptides; D008297:Male; D008875:Middle Aged; D010689:Phlebitis / Q000139:chemically induced; D016896:Treatment Outcome; D055815:Young Adult
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D001219:Aspartate Aminotransferases; D000469:Alkaline Phosphatase; D000077336:Caspofungin