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    Predicting the myelotoxicity of chemotherapy: the use of pretreatment O6-methylguanine-DNA methyltransferase determination in peripheral blood mononuclear cells.

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    Authors
    Sabharwal, A
    Waters, R
    Danson, Sarah
    Clamp, Andrew R
    Lorigan, Paul C
    Thatcher, Nick
    Margison, Geoffrey P
    Middleton, Mark R
    Affiliation
    Department of Medical Oncology, University of Oxford, Oxford, UK.
    Issue Date
    2011-12-21
    
    Metadata
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    Abstract
    To assess the value of pretreatment O-methylguanine-DNA methyltransferase (MGMT) expression in peripheral blood mononuclear cells (PBMCs) in predicting haematological toxicity with O-alkylating agent chemotherapy, we explored this relationship retrospectively in melanoma patients. Ninety-three patients treated with temozolomide or dacarbazine in four clinical trials were assessed, and a model of the interaction between MGMT expression and haematological toxicity was constructed. Nadir white-cell and platelet counts were related to, and hence could be predicted from, pretreatment MGMT. Leucopenia and thrombocytopenia were more prevalent amongst patients with low pretreatment MGMT, according to the highest grades of toxicity experienced and/or the dose intensity patients could sustain. Addition of interferon to chemotherapy or compression of the temozolomide schedule increased the toxicity. The model also predicts significant myelotoxicity where PBMC MGMT is inactivated, consistent with the experience in the clinic with lomeguatrib and O-benzylguanine. Determination of MGMT in PBMC can identify patients at greatest risk of toxicity or who are suitable for dose intensification.
    Citation
    Predicting the myelotoxicity of chemotherapy: the use of pretreatment O6-methylguanine-DNA methyltransferase determination in peripheral blood mononuclear cells. Melanoma Res. 2011 Dec;21(6):502-8
    Journal
    Melanoma Research
    URI
    http://hdl.handle.net/10541/85375
    DOI
    10.1097/CMR.0b013e32832ccd58
    PubMed ID
    19561552
    Type
    Article
    Language
    en
    ISSN
    1473-5636
    ae974a485f413a2113503eed53cd6c53
    10.1097/CMR.0b013e32832ccd58
    Scopus Count
    Collections
    All Christie Publications
    All Paterson Institute for Cancer Research
    Carcinogenesis Group
    Medical Oncology
    Medical Oncology
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