title: 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.affiliation: Department of Molecular Biology and Biochemistry, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, CA, USA.
authors.forename: P P
authors.initials: PP
authors.lastname: Grimminger
authors.forename: M
authors.initials: M
authors.lastname: Shi
authors.forename: C
authors.initials: C
authors.lastname: Barrett
authors.forename: D
authors.initials: D
authors.lastname: Lebwohl
authors.forename: K D
authors.initials: KD
authors.lastname: Danenberg
authors.forename: J
authors.initials: J
authors.lastname: Brabender
authors.forename: C L P
authors.initials: CL
authors.lastname: Vigen
authors.forename: P V
authors.initials: PV
authors.lastname: Danenberg
authors.forename: T
authors.initials: T
authors.lastname: Winder
authors.forename: H-J
authors.initials: HJ
authors.lastname: Lenz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D016019:Survival Analysis; D013940:Thymidylate Synthase / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D004268:DNA-Binding Proteins; D009944:Organoplatinum Compounds; D012333:RNA, Messenger; D013940:Thymidylate Synthase; C071447:ERCC1 protein, human; D004720:Endonucleases; D002955:Leucovorin; D005472:Fluorouracil