期刊
MELANOMA RESEARCH
卷 21, 期 6, 页码 502-508出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CMR.0b013e32832ccd58
关键词
dacarbazine; melanoma; O-6-methylguanine-DNA methyltransferase; temozolomide; toxicity
资金
- Cancer Research UK
- NIHR Biomedical Research Centre
To assess the value of pretreatment O-6-methylguanine-DNA methyltransferase (MGMT) expression in peripheral blood mononuclear cells (PBMCs) in predicting haematological toxicity with O-6-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-6-benzylguanine. Determination of MGMT in PBMC can identify patients at greatest risk of toxicity or who are suitable for dose intensification. Melanoma Res 21:502-508 (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.
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