JAC Advance Access originally published online on October 19, 2009
Journal of Antimicrobial Chemotherapy 2009 64(6):1274-1281; doi:10.1093/jac/dkp355
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Original research |
An EORTC Phase II study of caspofungin as first-line therapy of invasive aspergillosis in haematological patients
1 San Martino University Hospital, Genova, Italy 2 University Hospital, Strasbourg, France 3 Ankara University School of Medicine, Ankara, Turkey 4 EORTC, Brussels, Belgium 5 Cliniques Universitaires De Mont Godinne, Yvoir, Belgium 6 Ospedale Santa Croce, Cuneo, Italy 7 St Johannes Hospital Medizinische Klinik II, Duisburg, Germany 8 Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland 9 University Hospital, Barcelona, Spain 10 Institut Jules Bordet, Brussels, Belgium 11 Merck & Co., Inc., Whitehouse Station, NJ, USA 12 3rd Medical Department, Johannes Gutenberg University, Mainz, Germany 13 UZ Gasthuisberg, Leuven, Belgium
Received 11 June 2009; returned 11 July 2009; revised 3 September 2009; accepted 5 September 2009
* Corresponding author. Tel: +39-010-5600848; Fax: +39-010-5600264; E-mail: viscolic{at}unige.it
Objectives: Caspofungin was evaluated as first-line monotherapy of invasive aspergillosis (IA) in patients with haematological malignancies and undergoing autologous transplants.
Methods: Adults with proven or probable IA, defined strictly according to EORTC-MSG criteria, were eligible. Those with possible IA were enrolled, but were not evaluable for efficacy unless upgraded to proven/probable disease within 7 days of registration based on investigations performed within 48 h after enrolment. Caspofungin dosage was 70 mg (day 1) followed by 50 mg/day. The primary endpoint was the proportion of patients with complete or partial response at the end of caspofungin therapy in the modified intention to treat (MITT) group; secondary endpoints were response and survival at day 84 and safety.
Results: In the MITT group (n = 61), 75% of patients had cancer not in remission (relapsing or refractory), 85% were neutropenic at enrolment and 49% had a Karnofsky score of 
50. At end of treatment, 1 and 19 patients had complete and partial response, respectively [success rate 33% (20/61)], 9 (15%) achieved stabilization and 31 (51%) had disease progression. One patient was not evaluable. The 6 and 12 week survival rates were 66% (40/61) and 53% (32/60), respectively. Baseline characteristics associated with survival at day 84 were an underlying disease in remission (not relapsing or refractory) and Karnofsky score. Recovery from neutropenia at the end of treatment was also significantly associated with survival. No serious drug-related adverse events or discontinuations due to drug-related adverse events were observed.
Conclusions: Caspofungin provided an observed response rate compatible with the null hypothesis of a true response rate of 35%. Underlying disease-related factors had a major impact on results.
Keywords: acute leukaemia , fungal infections , echinocandins
Participants are listed in the Acknowledgements section.