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

• DOI: 10.1038/tpj.2011.29
• Publication Date: 2011-07-26T10:06:09Z
• 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
• Keywords: Adult; Aged, 80 and over; Male; Organoplatinum Compounds; Leucovorin; Thymidylate Synthase; Middle Aged; Endonucleases; Prognosis; Survival Analysis; 3. Good health; DNA-Binding Proteins; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; 0302 clinical medicine; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Humans; Female; Fluorouracil; RNA, Messenger; Neoplasm Metastasis; Aged

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.