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

2.50
Hdl Handle:
http://hdl.handle.net/10541/85375
Title:
Predicting the myelotoxicity of chemotherapy: the use of pretreatment O6-methylguanine-DNA methyltransferase determination in peripheral blood mononuclear cells.
Authors:
Sabharwal, A; Waters, R; Danson, Sarah; Clamp, Andrew R; Lorigan, Paul C ( 0000-0002-8875-2164 ) ; Thatcher, Nick; Margison, Geoffrey P; Middleton, Mark R
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.
Affiliation:
Department of Medical Oncology, University of Oxford, Oxford, UK.
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
Issue Date:
21-Dec-2011
URI:
http://hdl.handle.net/10541/85375
DOI:
10.1097/CMR.0b013e32832ccd58
PubMed ID:
19561552
Type:
Article
Language:
en
ISSN:
1473-5636
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research; Carcinogenesis Group; Medical Oncology; Medical Oncology; Early and Advance Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorSabharwal, Aen
dc.contributor.authorWaters, Ren
dc.contributor.authorDanson, Sarahen
dc.contributor.authorClamp, Andrew Ren
dc.contributor.authorLorigan, Paul Cen
dc.contributor.authorThatcher, Nicken
dc.contributor.authorMargison, Geoffrey Pen
dc.contributor.authorMiddleton, Mark Ren
dc.date.accessioned2009-11-05T10:19:50Z-
dc.date.available2009-11-05T10:19:50Z-
dc.date.issued2011-12-21-
dc.identifier.citationPredicting the myelotoxicity of chemotherapy: the use of pretreatment O6-methylguanine-DNA methyltransferase determination in peripheral blood mononuclear cells. Melanoma Res. 2011 Dec;21(6):502-8en
dc.identifier.issn1473-5636-
dc.identifier.pmid19561552-
dc.identifier.doi10.1097/CMR.0b013e32832ccd58-
dc.identifier.urihttp://hdl.handle.net/10541/85375-
dc.description.abstractTo 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.en
dc.languageENG-
dc.language.isoenen
dc.subjectChemotherapyen
dc.subjectMelanomaen
dc.subject.meshAntineoplastic Combined Chemotherapy Protocols-
dc.subject.meshBiomarkers, Pharmacological-
dc.subject.meshLeukocytes, Mononuclear-
dc.subject.meshMyeloid Cells-
dc.subject.mesh0(6)-Methylguanine-DNA Methyltransferase-
dc.titlePredicting the myelotoxicity of chemotherapy: the use of pretreatment O6-methylguanine-DNA methyltransferase determination in peripheral blood mononuclear cells.en
dc.typeArticleen
dc.contributor.departmentDepartment of Medical Oncology, University of Oxford, Oxford, UK.en
dc.identifier.journalMelanoma Researchen

Related articles on PubMed

All Items in Christie are protected by copyright, with all rights reserved, unless otherwise indicated.