O6-methylguanine-DNA methyltransferase in pretreatment tumour biopsies as a predictor of response to temozolomide in melanoma.

2.50
Hdl Handle:
http://hdl.handle.net/10541/92028
Title:
O6-methylguanine-DNA methyltransferase in pretreatment tumour biopsies as a predictor of response to temozolomide in melanoma.
Authors:
Middleton, Mark R; Lunn, J M; Morris, Charles; Rustin, G; Wedge, S R; Brampton, M H; Lind, Michael J; Lee, Siow Ming; Newell, D R; Bleehen, N M; Newlands, E S; Calvert, A H; Margison, Geoffrey P; Thatcher, Nick
Abstract:
Resistance of tumour cells to methylating and monochloroethylating agents in vitro and in vivo has been linked to levels of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT). In a clinical trial of temozolomide in advanced malignant melanoma, the relationship between pretreatment MGMT levels in biopsies of cutaneous tumours and involved lymph nodes and clinical response to the drug has been studied. Among 50 evaluable patients, there were three complete responses (CR), four partial responses (PR), six with stable disease (SD) and 37 with progressive disease (PD), with an overall response rate of 14%. In 33 patients in whom MGMT level and clinical response could be evaluated, the tumour MGMT levels (fmol mg(-1) protein) were: CR, 158 +/- 119; PR, 607 +/- 481; NC, 171 +/- 101; PD, 185 +/- 42.3. Thus, measurements of pretreatment levels of MGMT in melanoma did not predict for response to temozolomide.
Affiliation:
Department of Medical Oncology, Christie Hospital NHS Trust, Manchester, UK.
Citation:
O6-methylguanine-DNA methyltransferase in pretreatment tumour biopsies as a predictor of response to temozolomide in melanoma. 1998, 78 (9):1199-202 Br. J. Cancer
Journal:
British Journal of Cancer
Issue Date:
Nov-1998
URI:
http://hdl.handle.net/10541/92028
PubMed ID:
9820180
Type:
Article
Language:
en
ISSN:
0007-0920
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorMiddleton, Mark Ren
dc.contributor.authorLunn, J Men
dc.contributor.authorMorris, Charlesen
dc.contributor.authorRustin, Gen
dc.contributor.authorWedge, S Ren
dc.contributor.authorBrampton, M Hen
dc.contributor.authorLind, Michael Jen
dc.contributor.authorLee, Siow Mingen
dc.contributor.authorNewell, D Ren
dc.contributor.authorBleehen, N Men
dc.contributor.authorNewlands, E Sen
dc.contributor.authorCalvert, A Hen
dc.contributor.authorMargison, Geoffrey Pen
dc.contributor.authorThatcher, Nicken
dc.date.accessioned2010-02-12T15:49:39Z-
dc.date.available2010-02-12T15:49:39Z-
dc.date.issued1998-11-
dc.identifier.citationO6-methylguanine-DNA methyltransferase in pretreatment tumour biopsies as a predictor of response to temozolomide in melanoma. 1998, 78 (9):1199-202 Br. J. Canceren
dc.identifier.issn0007-0920-
dc.identifier.pmid9820180-
dc.identifier.urihttp://hdl.handle.net/10541/92028-
dc.description.abstractResistance of tumour cells to methylating and monochloroethylating agents in vitro and in vivo has been linked to levels of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT). In a clinical trial of temozolomide in advanced malignant melanoma, the relationship between pretreatment MGMT levels in biopsies of cutaneous tumours and involved lymph nodes and clinical response to the drug has been studied. Among 50 evaluable patients, there were three complete responses (CR), four partial responses (PR), six with stable disease (SD) and 37 with progressive disease (PD), with an overall response rate of 14%. In 33 patients in whom MGMT level and clinical response could be evaluated, the tumour MGMT levels (fmol mg(-1) protein) were: CR, 158 +/- 119; PR, 607 +/- 481; NC, 171 +/- 101; PD, 185 +/- 42.3. Thus, measurements of pretreatment levels of MGMT in melanoma did not predict for response to temozolomide.en
dc.language.isoenen
dc.subject.meshAdult-
dc.subject.meshAntineoplastic Agents, Alkylating-
dc.subject.meshBiopsy-
dc.subject.meshDacarbazine-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshLeukocytes, Mononuclear-
dc.subject.meshLymphatic Metastasis-
dc.subject.meshMale-
dc.subject.meshMelanoma-
dc.subject.meshMiddle Aged-
dc.subject.meshO(6)-Methylguanine-DNA Methyltransferase-
dc.subject.meshPredictive Value of Tests-
dc.subject.meshProspective Studies-
dc.titleO6-methylguanine-DNA methyltransferase in pretreatment tumour biopsies as a predictor of response to temozolomide in melanoma.en
dc.typeArticleen
dc.contributor.departmentDepartment of Medical Oncology, Christie Hospital NHS Trust, Manchester, UK.en
dc.identifier.journalBritish Journal of Canceren

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