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Infectious Complications

Caspofungin first-line therapy for invasive aspergillosis in allogeneic hematopoietic stem cell transplant patients: an European Organisation for Research and Treatment of Cancer study

Bone Marrow Transplantation volume 45, pages 1227–1233 (2010)Cite this article

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Abstract

Caspofungin at standard dose was evaluated as first-line monotherapy of mycologically documented probable/proven invasive aspergillosis (IA) (unmodified European Organisation for Research and Treatment of Cancer/Mycosis Study Group criteria) in allogeneic hematopoietic SCT patients. The primary efficacy end point was complete or partial response at end of caspofungin treatment. Response at week 12, survival and safety were additional end points. Enrollment was stopped prematurely because of low accrual, with 42 enrolled and 24 eligible, giving the study a power of 85%. Transplant was from unrelated donors in 16 patients; acute or chronic GVHD was present in 15. In all, 12 patients were neutropenic (<500/μl) at baseline, 10 received steroids and 16 calcineurin inhibitors or sirolimus. Median duration of caspofungin treatment was 24 days. At the end of caspofungin therapy, 10 (42%) patients had complete or partial response (95% confidence interval: 22–63%); 1 (4%) and 12 (50%) had stable and progressing disease, respectively; one was not evaluable. At week 12, eight patients (33%) had complete or partial response. Survival rates at week 6 and 12 were 79 and 50%, respectively. No patient had a drug-related serious adverse event or discontinued because of toxicity. Caspofungin first-line therapy was effective and well tolerated in allogeneic hematopoietic SCT patients with mycologically documented IA.

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Acknowledgements

We thank Wendy Horn, PhD for writing and editorial assistance, which was funded by Merck & Co, Inc. Presented in part as a poster at the 48th Annual Meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy, 25–28 October 2008, Washington, DC.

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Authors and Affiliations

  1. Department of Oncology and Hematology, Hôpital de Hautepierre, Strasbourg, France

    R Herbrecht

  2. Department of Hematology, Acute Leukemia and Transplantation Unit, Universitaire Ziekenhuizen Leuven, Campus Gasthuisberg, Leuven, Belgium

    J Maertens

  3. European Organization for Research and Treatment of Cancer (EORTC), Brussels, Belgium

    L Baila, L Meert & M Paesmans

  4. Jules Bordet Institute, Free University of Brussels, Brussels, Belgium

    M Aoun & L Ameye

  5. Department of Internal Medicine II, Division of Infectious Diseases, University of Wuerzburg Medical Center, Würzburg, Germany

    W Heinz

  6. Servicio de Hematología, Hospital de la Santa Creu i Sant Pau, Universitat Autónoma de Barcelona, Barcelona, Spain

    R Martino

  7. Department of Hematology and Oncology, Charité B. Franklin, Berlin, Germany

    S Schwartz

  8. Universitätsmedizin, Johannes Gutenberg-University, Mainz, Germany

    A J Ullmann

  9. Department of Medicine, Infectious Diseases Service, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland

    O Marchetti

  10. Department of Hematology and Stem Cell Transplantation Unit, Ankara University Medical School, Cebeci Campus, Cebeci, Ankara, Turkey

    H Akan

  11. Merck & Co, White House Station, NJ, USA

    M Shivaprakash

  12. Division of Infectious Disease, San Martino University Hospital, University of Genova, Genova, Italy

    C Viscoli

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for the Infectious Diseases Group of the EORTC

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Correspondence to R Herbrecht.

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Competing interests

R Herbrecht has been a consultant or received honoraria or a grant from Astellas, Basilea, Gilead, Merck & Co, Novartis, Pfizer, Schering Plough, and Zeneus. J Maertens has been a consultant or received honoraria or a grant from Astellas, Gilead, Merck & Co, Pfizer, Schering Plough, Zeneus, Bio-Rad Laboratories, Myconostica and Basilea Pharmaceuticals. M Aoun has been a consultant or received honoraria or a grant from Pfizer, Schering-Plough and Merck & Co. W Heinz has been a consultant or received honoraria or a grant from Essex/Schering-Plough, Gilead, Merck & Co and Pfizer. S Schwartz has received travel grants and honoraria from Pfizer and Enzon. AJ Ullmann has received funds for speaking at symposia organized on behalf of Astellas, Gilead, Merck & Co, Pfizer, Schering Plough, and MSD, has also received funds for research from MSD, Schering-Plough, and Astellas and is a member of the MSD advisory board for caspofungin and further is a member of the advisory boards from Astellas, Basilea, Gilead, Aicuris, Pfizer, and Schering Plough. O Marchetti received research grants and honoraria as a consultant and/or speaker from Merck & Co, Novartis, Pfizer and Schering-Plough. H Akan has received travel grants and honoraria from MSD and Pfizer. M Shivaprakash is employed by Merck & Co, Inc. C Viscoli has been a consultant to Astellas, Gilead, Merck & Co, Pfizer, Schering-Plough, has been member of speaker’s bureaus for Gilead, Pfizer, Schering-Plough and has received research grant from Pfizer, Merck & Co, Gilead, BMS and Abbott. L Baila, L Ameye, L Meert, M Paesmans and R Martino declare no conflict of interest.

Data Review Committee: H Akan, L Baila, R Herbrecht (chairman), O Marchetti, R Martino, L Meert (data manager), M Paesmans (statistician) and AJ Ullmann.

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Herbrecht, R., Maertens, J., Baila, L. et al. Caspofungin first-line therapy for invasive aspergillosis in allogeneic hematopoietic stem cell transplant patients: an European Organisation for Research and Treatment of Cancer study. Bone Marrow Transplant 45, 1227–1233 (2010). https://doi.org/10.1038/bmt.2009.334

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