No influence of the polymorphisms CYP2C19 and CYP2D6 on the efficacy of cyclophosphamide, thalidomide, and bortezomib in patients with Multiple Myeloma

Annette Juul Vangsted, Karen Søeby, Tobias Klausen, Niels Abildgaard , Niels Frost Andersen, Peter Gimsing, Henrik Gregersen, Ulla Vogel, Thomas Werge, Henrik B. Rasmussen

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    Resumé

    Background
    The response to treatment varies among patients with multiple myeloma and markers for prediction of treatment outcome are highly needed. Bioactivation of cyclophosphamide and thalidomide, and biodegradation of bortezomib, is dependent on cytochrome P450 metabolism. We explored the potential influence of different polymorphisms in the CYP enzymes on the outcome of treatment.

    Methods
    Data was analyzed from 348 patients undergoing high-dose treatment and stem cell support in Denmark in 1994 to 2004. Clinical information on relapse treatment in 243 individual patients was collected. The patients were genotyped for the non-functional alleles CYP2C19*2 and CYP2D6*3, *4, *5 (gene deletion), *6, and CYP2D6 gene duplication.

    Results
    In patients who were treated with bortezomib and were carriers of one or two defective CYP2D6 alleles there was a trend towards a better time-to-next treatment. We found no association between the number of functional CYP2C19 and CYP2D6 alleles and outcome of treatment with cyclophosphamide or thalidomide. Neither was the number of functional CYP2C19 and CYP2D6 alleles associated with neurological adverse reactions to thalidomide and bortezomib.

    Conclusion
    There was no association between functional CYP2C19 and CYP2D6 alleles and treatment outcome in multiple myeloma patients treated with cyclophosphamide, thalidomide or bortezomib. A larger number of patients treated with bortezomib are needed to determine the role of CYP2D6 alleles in treatment outcome.
    OriginalsprogEngelsk
    TidsskriftBMC Cancer
    Vol/bind10
    Udgave nummer404
    Antal sider8
    ISSN1471-2407
    DOI
    StatusUdgivet - 2010

    Citer dette

    Vangsted, Annette Juul ; Søeby, Karen ; Klausen, Tobias ; Abildgaard , Niels ; Andersen, Niels Frost ; Gimsing, Peter ; Gregersen, Henrik ; Vogel, Ulla ; Werge, Thomas ; Rasmussen, Henrik B. / No influence of the polymorphisms CYP2C19 and CYP2D6 on the efficacy of cyclophosphamide, thalidomide, and bortezomib in patients with Multiple Myeloma. I: BMC Cancer. 2010 ; Bind 10, Nr. 404.
    @article{281599b8be074ca7be86589d7aadfdff,
    title = "No influence of the polymorphisms CYP2C19 and CYP2D6 on the efficacy of cyclophosphamide, thalidomide, and bortezomib in patients with Multiple Myeloma",
    abstract = "Background The response to treatment varies among patients with multiple myeloma and markers for prediction of treatment outcome are highly needed. Bioactivation of cyclophosphamide and thalidomide, and biodegradation of bortezomib, is dependent on cytochrome P450 metabolism. We explored the potential influence of different polymorphisms in the CYP enzymes on the outcome of treatment. Methods Data was analyzed from 348 patients undergoing high-dose treatment and stem cell support in Denmark in 1994 to 2004. Clinical information on relapse treatment in 243 individual patients was collected. The patients were genotyped for the non-functional alleles CYP2C19*2 and CYP2D6*3, *4, *5 (gene deletion), *6, and CYP2D6 gene duplication. Results In patients who were treated with bortezomib and were carriers of one or two defective CYP2D6 alleles there was a trend towards a better time-to-next treatment. We found no association between the number of functional CYP2C19 and CYP2D6 alleles and outcome of treatment with cyclophosphamide or thalidomide. Neither was the number of functional CYP2C19 and CYP2D6 alleles associated with neurological adverse reactions to thalidomide and bortezomib. Conclusion There was no association between functional CYP2C19 and CYP2D6 alleles and treatment outcome in multiple myeloma patients treated with cyclophosphamide, thalidomide or bortezomib. A larger number of patients treated with bortezomib are needed to determine the role of CYP2D6 alleles in treatment outcome.",
    author = "Vangsted, {Annette Juul} and Karen S{\o}eby and Tobias Klausen and Niels Abildgaard and Andersen, {Niels Frost} and Peter Gimsing and Henrik Gregersen and Ulla Vogel and Thomas Werge and Rasmussen, {Henrik B.}",
    year = "2010",
    doi = "10.1186/1471-2407-10-404",
    language = "English",
    volume = "10",
    journal = "B M C Cancer",
    issn = "1471-2407",
    publisher = "BioMed Central Ltd.",
    number = "404",

    }

    Vangsted, AJ, Søeby, K, Klausen, T, Abildgaard , N, Andersen, NF, Gimsing, P, Gregersen, H, Vogel, U, Werge, T & Rasmussen, HB 2010, 'No influence of the polymorphisms CYP2C19 and CYP2D6 on the efficacy of cyclophosphamide, thalidomide, and bortezomib in patients with Multiple Myeloma', BMC Cancer, bind 10, nr. 404. https://doi.org/10.1186/1471-2407-10-404

    No influence of the polymorphisms CYP2C19 and CYP2D6 on the efficacy of cyclophosphamide, thalidomide, and bortezomib in patients with Multiple Myeloma. / Vangsted, Annette Juul; Søeby, Karen; Klausen, Tobias; Abildgaard , Niels; Andersen, Niels Frost; Gimsing, Peter; Gregersen, Henrik; Vogel, Ulla; Werge, Thomas; Rasmussen, Henrik B.

    I: BMC Cancer, Bind 10, Nr. 404, 2010.

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    TY - JOUR

    T1 - No influence of the polymorphisms CYP2C19 and CYP2D6 on the efficacy of cyclophosphamide, thalidomide, and bortezomib in patients with Multiple Myeloma

    AU - Vangsted, Annette Juul

    AU - Søeby, Karen

    AU - Klausen, Tobias

    AU - Abildgaard , Niels

    AU - Andersen, Niels Frost

    AU - Gimsing, Peter

    AU - Gregersen, Henrik

    AU - Vogel, Ulla

    AU - Werge, Thomas

    AU - Rasmussen, Henrik B.

    PY - 2010

    Y1 - 2010

    N2 - Background The response to treatment varies among patients with multiple myeloma and markers for prediction of treatment outcome are highly needed. Bioactivation of cyclophosphamide and thalidomide, and biodegradation of bortezomib, is dependent on cytochrome P450 metabolism. We explored the potential influence of different polymorphisms in the CYP enzymes on the outcome of treatment. Methods Data was analyzed from 348 patients undergoing high-dose treatment and stem cell support in Denmark in 1994 to 2004. Clinical information on relapse treatment in 243 individual patients was collected. The patients were genotyped for the non-functional alleles CYP2C19*2 and CYP2D6*3, *4, *5 (gene deletion), *6, and CYP2D6 gene duplication. Results In patients who were treated with bortezomib and were carriers of one or two defective CYP2D6 alleles there was a trend towards a better time-to-next treatment. We found no association between the number of functional CYP2C19 and CYP2D6 alleles and outcome of treatment with cyclophosphamide or thalidomide. Neither was the number of functional CYP2C19 and CYP2D6 alleles associated with neurological adverse reactions to thalidomide and bortezomib. Conclusion There was no association between functional CYP2C19 and CYP2D6 alleles and treatment outcome in multiple myeloma patients treated with cyclophosphamide, thalidomide or bortezomib. A larger number of patients treated with bortezomib are needed to determine the role of CYP2D6 alleles in treatment outcome.

    AB - Background The response to treatment varies among patients with multiple myeloma and markers for prediction of treatment outcome are highly needed. Bioactivation of cyclophosphamide and thalidomide, and biodegradation of bortezomib, is dependent on cytochrome P450 metabolism. We explored the potential influence of different polymorphisms in the CYP enzymes on the outcome of treatment. Methods Data was analyzed from 348 patients undergoing high-dose treatment and stem cell support in Denmark in 1994 to 2004. Clinical information on relapse treatment in 243 individual patients was collected. The patients were genotyped for the non-functional alleles CYP2C19*2 and CYP2D6*3, *4, *5 (gene deletion), *6, and CYP2D6 gene duplication. Results In patients who were treated with bortezomib and were carriers of one or two defective CYP2D6 alleles there was a trend towards a better time-to-next treatment. We found no association between the number of functional CYP2C19 and CYP2D6 alleles and outcome of treatment with cyclophosphamide or thalidomide. Neither was the number of functional CYP2C19 and CYP2D6 alleles associated with neurological adverse reactions to thalidomide and bortezomib. Conclusion There was no association between functional CYP2C19 and CYP2D6 alleles and treatment outcome in multiple myeloma patients treated with cyclophosphamide, thalidomide or bortezomib. A larger number of patients treated with bortezomib are needed to determine the role of CYP2D6 alleles in treatment outcome.

    U2 - 10.1186/1471-2407-10-404

    DO - 10.1186/1471-2407-10-404

    M3 - Journal article

    VL - 10

    JO - B M C Cancer

    JF - B M C Cancer

    SN - 1471-2407

    IS - 404

    ER -