TY - JOUR
T1 - Liposomal amphotericin B in combination with caspofungin for invasive aspergillosis in patients with hematologic malignancies
T2 - A randomized pilot study (combistrat trial)
AU - Caillot, Denis
AU - Thiébaut, Anne
AU - Herbrecht, Raoul
AU - De Botton, Stéphane
AU - Pigneux, Arnaud
AU - Bernard, Frédéric
AU - Larché, Jérôme
AU - Monchecourt, Françoise
AU - Alfandari, Serge
AU - Mahi, Lamine
PY - 2007/12/15
Y1 - 2007/12/15
N2 - BACKGROUND. Invasive aspergillosis (IA) has a poor prognosis in immunocompromised patients. Combinations of drugs that act on different targets are expected to improve the clinical efficacy of separate compounds. METHODS. Patients with proven or probable IA were randomized in a prospective, open pilot study to receive either a combination of liposomal amphotericin B (AmB) at the standard dose (3 mg/kg daily) and caspofungin at the standard dose or monotherapy with a high-dose AmB regimen (10 mg/kg daily). RESULTS. Thirty patients (21 men and 9 women) with hematologic malignancies were analyzed, and there were 15 patients in each arm. The median duration of treatment was 18 days for the combination group and 17 days for the high-dose monotherapy group. At the end of treatment, there were significantly more favorable overall responses (partial or complete responses; P = .028) in the combination group (10 of 15 patients; 67%) compared with the high-dose monotherapy group (4 of 15 patients; 27%). Survival rates at 12 weeks after inclusion were 100% and 80%, respectively. Infusion-related reactions occurred in 3 patients in the high-dose monotherapy group. A 2-fold increase in serum creatinine occurred in 4 of 17 patients (23%) who received high-dose monotherapy and 1 of 15 patient (7%) who received combination therapy; hypokalemia <3 mmol/L occurred in 3 patients and 2 patients, respectively. CONCLUSIONS. The combination of liposomal AmB and caspofungin was promising as therapy for IA compared with monotherapy. A trial that includes more patients will be required next to confirm the results of this pilot study.
AB - BACKGROUND. Invasive aspergillosis (IA) has a poor prognosis in immunocompromised patients. Combinations of drugs that act on different targets are expected to improve the clinical efficacy of separate compounds. METHODS. Patients with proven or probable IA were randomized in a prospective, open pilot study to receive either a combination of liposomal amphotericin B (AmB) at the standard dose (3 mg/kg daily) and caspofungin at the standard dose or monotherapy with a high-dose AmB regimen (10 mg/kg daily). RESULTS. Thirty patients (21 men and 9 women) with hematologic malignancies were analyzed, and there were 15 patients in each arm. The median duration of treatment was 18 days for the combination group and 17 days for the high-dose monotherapy group. At the end of treatment, there were significantly more favorable overall responses (partial or complete responses; P = .028) in the combination group (10 of 15 patients; 67%) compared with the high-dose monotherapy group (4 of 15 patients; 27%). Survival rates at 12 weeks after inclusion were 100% and 80%, respectively. Infusion-related reactions occurred in 3 patients in the high-dose monotherapy group. A 2-fold increase in serum creatinine occurred in 4 of 17 patients (23%) who received high-dose monotherapy and 1 of 15 patient (7%) who received combination therapy; hypokalemia <3 mmol/L occurred in 3 patients and 2 patients, respectively. CONCLUSIONS. The combination of liposomal AmB and caspofungin was promising as therapy for IA compared with monotherapy. A trial that includes more patients will be required next to confirm the results of this pilot study.
KW - Antifungal treatment
KW - Caspofungin
KW - Drug combination
KW - Invasive aspergillosis
KW - Liposomal amphotericin B
UR - http://www.scopus.com/inward/record.url?scp=37049003816&partnerID=8YFLogxK
U2 - 10.1002/cncr.23109
DO - 10.1002/cncr.23109
M3 - Article
C2 - 17941026
AN - SCOPUS:37049003816
SN - 0008-543X
VL - 110
SP - 2740
EP - 2746
JO - Cancer
JF - Cancer
IS - 12
ER -