Grimminger, P. P., Shi, M., Barrett, C., Lebwohl, D., Danenberg, K. D., Brabender, J., Vigen, C. L. P., Danenberg, P. V., Winder, T. and Lenz, H-J (2012). TS and ERCC-1 mRNA expressions and clinical outcome in patients with metastatic colon cancer in CONFIRM-1 and-2 clinical trials. Pharmacogenomics J., 12 (5). S. 404 - 412. LONDON: NATURE PUBLISHING GROUP. ISSN 1473-1150

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Abstract

To validate established cutoff levels of thymidylate synthase (TS) and excision repair cross-complementing (ERCC-1) intratumoral mRNA expressions in tumor samples from metastatic colorectal cancer (mCRC) patients treated with PTK787/ZK222584 (PTK/ZK). From 122 samples of patients with mCRC enrolled in CONFIRM-1 (Colorectal Oral Novel Therapy for the Inhibition of Angiogenesis and Retarding of Metastases) or CONFIRM-2, mRNA was isolated of microdissected formalin-fixed paraffin-embedded samples and quantitated using TaqMan-based technology. Existing TS and ERCC-1 cutoff levels were tested for their prognostic value in first-line and second-line therapy. TS expression was associated with overall survival (OS) in first-line, but not second-line therapy. ERCC-1 was associated with OS in patients treated with first-line and second-line FOLFOX4. In first-line FOLFOX4, combination of high TS and/or high ERCC-1 was associated with shorter OS. A correlation was observed between ERCC-1 expression and benefit from PTK/ZK_FOLFOX4 treatment. TS and ERCC-1 expression is associated with clinical outcome in mCRC. Baseline TS and ERCC-1 levels may allow the selection of patients who benefit from FOLFOX4 chemotherapy. The Pharmacogenomics Journal (2012) 12, 404-411; doi:10.1038/tpj.2011.29; published online 26 July 2011

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Grimminger, P. P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shi, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barrett, C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lebwohl, D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Danenberg, K. D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brabender, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vigen, C. L. P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Danenberg, P. V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Winder, T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lenz, H-JUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-482589
DOI: 10.1038/tpj.2011.29
Journal or Publication Title: Pharmacogenomics J.
Volume: 12
Number: 5
Page Range: S. 404 - 412
Date: 2012
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 1473-1150
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
THYMIDYLATE SYNTHASE EXPRESSION; NUCLEOTIDE EXCISION-REPAIR; COLORECTAL-CANCER; GENE-EXPRESSION; DIHYDROPYRIMIDINE DEHYDROGENASE; PREOPERATIVE CHEMORADIOTHERAPY; PROTRACTED-INFUSION; PROGNOSTIC VALUE; FLUOROURACIL; SURVIVALMultiple languages
Genetics & Heredity; Pharmacology & PharmacyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/48258

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