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Conditioning Regimens

Busulfex (i.v. BU) and CY regimen before SCT: Japanese-targeted phase II pharmacokinetics combined study

Bone Marrow Transplantation volume 43, pages 611–617 (2009)Cite this article

Abstract

To evaluate the toxicity and efficacy of an i.v. preparation of BU (12.8 mg/kg), combined with CY (120 mg/kg), a prospective study was performed on 30 Japanese patients (median age, 30 years) with hematologic malignancies undergoing hematopoietic SCT (28 allogeneic transplants from an HLA-matched donor and 2 autologous transplants). There were no significant toxicities, and all but one patient showed evidence of granulocyte engraftment at a median of 14 days for allogeneic and 11 days for autologous transplantation. Grades II–IV acute and chronic GVHD occurred in 9 (9/27, 33%) and 16 patients (16/27, 59%), respectively. Non-relapse mortality at days 100 and 365 was 3 and 17%, respectively. The pharmacokinetics of i.v. BU showed close inter- and intrapatient consistency; the area under the plasma concentration–time curve of the first administration remained at less than 1500 μmol min/l in 27 of the 29 patients (93%), and between 900 and 1350 μmol min/l in 22 patients (73%). As all of the profiles overlap with data from non-Japanese patients, we conclude that racial factors may not seriously influence the bioactivity of i.v. BU.

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Acknowledgements

We thank Kirin Pharma Co. Ltd. (Japan) and PDL Bio Pharma Inc. (USA) for their support for this study. This study was conducted as a pivotal trial supported by Kirin Pharma Co. Ltd., Tokyo, Japan.

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Authors and Affiliations

  1. Hematology and Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan

    S-W Kim, S-i Mori, R Tanosaki, T Fukuda & Y Takaue

  2. Division of Exploratory Research, Institute of Medical Science, University of Tokyo, Tokyo, Japan

    M Kami

  3. Department of Hematology, Komagome Hospital, Tokyo, Japan

    H Sakamaki & T Yamashita

  4. Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan

    Y Kodera

  5. Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    S Terakura

  6. Department of Hematology, Toranomon Hospital, Tokyo, Japan

    S Taniguchi

  7. Department of Hematology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan

    S Miyakoshi

  8. Division of Clinical Oncology and Hematology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan

    N Usui & S Yano

  9. Department of Pediatrics, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan

    Y Kawano

  10. Section of Pediatrics, National Kyushu Cancer Center, Fukuoka, Japan

    Y Nagatoshi

  11. National Omuta Hospital, Omuta, Japan

    M Harada

  12. Department of Hematology and Cell Therapy, Aichi Cancer Center Hospital, Nagoya, Japan

    Y Morishima

  13. Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan

    S Okamoto

  14. Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan

    A M Saito

  15. Department of Biostatistics/Epidemiology and Preventive Health Sciences, School of Health Sciences and Nursing, University of Tokyo, Tokyo, Japan

    A M Saito & Y Ohashi

  16. Department of Internal Medicine and Molecular Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

    R Ueda

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  1. S-W Kim
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  16. M Harada
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  19. A M Saito
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  20. Y Ohashi
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  21. R Ueda
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  22. Y Takaue
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Correspondence to Y Takaue.

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Kim, SW., Mori, Si., Tanosaki, R. et al. Busulfex (i.v. BU) and CY regimen before SCT: Japanese-targeted phase II pharmacokinetics combined study. Bone Marrow Transplant 43, 611–617 (2009). https://doi.org/10.1038/bmt.2008.372

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  • DOI: https://doi.org/10.1038/bmt.2008.372

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