TS and ERCC-1 mRNA expressions and clinical outcome in patients with metastatic colon cancer in CONFIRM-1 and -2 clinical trials.

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.

• Authors: P P Grimminger, M Shi, C Barrett, D Lebwohl, K D Danenberg, J Brabender, C L P Vigen, P V Danenberg, T Winder, H-J Lenz
• Journal: The pharmacogenomics journal (Pharmacogenomics J) Vol. 12 Issue 5 Pg. 404-11 (Oct 2012) ISSN: 1473-1150 [Electronic] United States
• PMID: 21788964 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• DNA-Binding Proteins
• Organoplatinum Compounds
• RNA, Messenger
• Thymidylate Synthase
• ERCC1 protein, human
• Endonucleases
• Leucovorin
• Fluorouracil

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Colonic Neoplasms (drug therapy, pathology)
• DNA-Binding Proteins (genetics, metabolism)
• Endonucleases (genetics, metabolism)
• Female
• Fluorouracil (administration & dosage)
• Gene Expression Regulation, Neoplastic (drug effects, genetics)
• Humans
• Leucovorin (administration & dosage)
• Male
• Middle Aged
• Neoplasm Metastasis
• Organoplatinum Compounds (administration & dosage)
• Prognosis
• RNA, Messenger (metabolism)
• Survival Analysis
• Thymidylate Synthase (genetics, metabolism)
• Treatment Outcome