Predicting the myelotoxicity of chemotherapy: the use of pretreatment O6-methylguanine-DNA methyltransferase determination in peripheral blood mononuclear cells.
Authors
Sabharwal, AWaters, 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
Show full item recordAbstract
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):502-8Journal
Melanoma ResearchDOI
10.1097/CMR.0b013e32832ccd58PubMed ID
19561552Type
ArticleLanguage
enISSN
1473-5636ae974a485f413a2113503eed53cd6c53
10.1097/CMR.0b013e32832ccd58
Scopus Count
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