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Liposomal amphotericin B in combination with caspofungin for invasive aspergillosis in patients with hematologic malignancies
Author(s) -
Caillot Denis,
Thiébaut Anne,
Herbrecht Raoul,
de Botton Stéphane,
Pigneux Arnaud,
Bernard Frédéric,
Larché Jérôme,
Monchecourt Françoise,
Alfandari Serge,
Mahi Lamine
Publication year - 2007
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.23109
Subject(s) - medicine , caspofungin , combination therapy , regimen , hypokalemia , aspergillosis , gastroenterology , amphotericin b , creatinine , surgery , antifungal , immunology , dermatology
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. Cancer 2007. © 2007 American Cancer Society.