A phase II dose escalation study of caspofungin for invasive aspergillosis

Ref ID: 18582

Author:

O. Cornely (1), J.J. Vehreschild (1), M. Rüping (1), D. Arenz
(1), S. Schwartz (2), C.P. Heussel (3), G. Silling (4), M. Mahne
(1), J. Franklin (1), U. Harnischmacher (1), A. Wilkens (1),
F. Farowski (1), M. Karthaus (5), T. Lehrnbecher (6), A.

Author address:

(1)University of Cologne (Cologne, DE); (2)Charité Campus
Benjamin Franklin (Berlin, DE); (3)University Hospital
Heidelberg (Heidelberg, DE); (4)University of Munster (Munster,
DE); (5)Klinikum Neuperlach (Munich, DE); (6)University of
Frankf

Full conference title:

Annual Meeting of the EBMT, 36th

Abstract:

Objectives: Treatment of invasive aspergillosis (IA) fails in up to
50% and mortality is at least 30%. Antifungal combination treatment has not been proven to be benefi cial and dose escalation
with liposomal amphotericin B did not improve outcome. New
approaches are needed.
Methods: High dose caspofungin was investigated in an escalating Fibonacci approach in IA defi ned according to modifi ed S219
EORTC/MSG criteria. In cohorts at 70 mg, 100 mg, 150 mg, or
200 mg QD, 8 patients each were to receive caspofungin fi rst-line
treatment for proven/probable IA for up to 28 days. Dose limiting
toxicity was defi ned as 2 of 8 patients in the same cohort with the
same grade ≥ 4 non-haematological treatment-related adverse
event (TRAE), or 4 of 8 patients with a grade ≥ = 3 non-haematological TRAE. If no dose-limiting toxicity was reached, 12 additional
patients were enrolled in the 200 mg cohort. Patients unevaluable
for toxicity or pharmacokinetic analysis were replaced.
Results: A total of 46 patients were treated in the 4 cohorts (9,
8, 9, 20 pts). IA was proven in 2.2% and probable in 97.8%.
Patient characteristics were as follows: Median age 61 years
(min 18.3, max 73.7); 21/46 (45.7%) female. Underlying diseases distribution was: AML 50%, ALL 8.7%, lymphoma 19.6%,
chronic lymphocytic leukaemia 10.9%, other 10.9%. Median
duration of treatment was 24.5 days. Two (4.3%) patients with
treatment durations 8804; 5 days were replaced for pharmacokinetic
analysis, but evaluated for safety and effi cacy. No dose-limiting toxicity was found by investigator or DSMB assessment.
At end of treatment (EOT) complete plus partial response,
was achieved in the 4 cohorts in 4/9, 3/8, 6/9, 12/20 patients,
i.e. 25/46 (54.3%) of the total population. Stable disease was
achieved in 4 patients (8.7%), 17 (37%) patients failed treatment. Overall survival at 12 weeks was 76.1%. After a 12 week
follow-up attributable mortality was 8.7%. Death due to malignancy occurred in 10.9%, to sepsis in 8.7%.
Conclusions: In the fi rst-line treatment of proven or probable
invasive aspergillosis no dose-limiting toxicity of caspofungin
at doses up to 200 mg QD was found. Complete plus partial
response rates at EOT were 54.3% after dose-escalated caspofungin treatment, and thus in the range of the success rates
previously reported with voriconazole and liposomal amphotericin B. Twelve weeks after start of treatment the 23.9% overall
mortality was lower than found in the literature.

Abstract Number: P747

Conference Year: 2010

Link to conference website: NULL

New link: NULL

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