Universität zu Köln

Cornely, O. A., Vehreschild, J. J., Vehreschild, M. J. G. T., Wuerthwein, G., Arenz, D., Schwartz, S., Heussel, C. P., Silling, G., Mahne, M., Franklin, J., Harnischmacher, U., Wilkens, A., Farowski, F., Karthaus, M., Lehrnbecher, T., Ullmann, A. J., Hallek, M. and Groll, A. H. (2011). Phase II Dose Escalation Study of Caspofungin for Invasive Aspergillosis. Antimicrob. Agents Chemother., 55 (12). S. 5798 - 5804. WASHINGTON: AMER SOC MICROBIOLOGY. ISSN 0066-4804

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Abstract

Our objective was to evaluate the maximum tolerated dose of caspofungin for invasive aspergillosis (IA). The safety and pharmacokinetics of escalating dosages of caspofungin were investigated in IA. Eight patients each received caspofungin 70, 100, 150, or 200 mg once a day (QD). Dose-limiting toxicity (DLT) was defined as the same non-hematological treatment-related adverse event of grade >= 4 in 2 of 8 patients or >= 3 in 4 of 8 patients in a cohort. A total of 46 patients (median age, 61 years; 21 female; 89% with hematological malignancies) received caspofungin (9, 8, 9, and 20 patients in the 70-, 100-, 150-, and 200-mg cohorts) for a median of 24.5 days. Plasma pharmacokinetics were linear across the investigated dosages and followed a two-compartment model, with weight as the covariate on clearance and sex as the covariate on central volume of distribution. Simulated peak plasma concentrations at steady state ranged from 14.2 to 40.6 mg/liter (28%), trough concentrations from 4.1 to 11.8 mg/liter (58%), and area under the concentration-time curve from 175 to 500 mg/liter/h (32%) (geometric mean, geometric coefficient of variation). Treatment was well tolerated without dose-limiting toxicity. The rate of complete or partial responses was 54.3%, and the overall mortality at 12-week follow-up was 28.3%. In first-line treatment of invasive aspergillosis, daily doses of up to 200 mg caspofungin were well tolerated and the maximum tolerated dose was not reached. Pharmacokinetics was linear. Response rates were similar to those previously reported for voriconazole and liposomal amphotericin.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Cornely, O. A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Vehreschild, J. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Vehreschild, M. J. G. T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wuerthwein, G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Arenz, D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schwartz, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Heussel, C. P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Silling, G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mahne, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Franklin, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Harnischmacher, U. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wilkens, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Farowski, F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Karthaus, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lehrnbecher, T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ullmann, A. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hallek, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Groll, A. H. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-484668
DOI:	10.1128/AAC.05134-11
Journal or Publication Title:	Antimicrob. Agents Chemother.
Volume:	55
Number:	12
Page Range:	S. 5798 - 5804
Date:	2011
Publisher:	AMER SOC MICROBIOLOGY
Place of Publication:	WASHINGTON
ISSN:	0066-4804
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language LIPOSOMAL AMPHOTERICIN-B; WORKING-PARTY AGIHO; DOUBLE-BLIND; FUNGAL-INFECTIONS; PULMONARY ASPERGILLOSIS; EUROPEAN ORGANIZATION; RANDOMIZED-TRIAL; 1ST-LINE THERAPY; ONCOLOGY DGHO; MULTICENTER Multiple languages Microbiology; Pharmacology & Pharmacy Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48466