title: Expression of genes related to activity of oxaliplatin and 5-fluorouracil in endoscopic biopsies of primary esophageal cancer in patients receiving oxaliplatin, 5-flourouracil and radiation: characterization and exploratory analysis with survival.
abstract: With a goal of identifying relations between gene expression and response (mucosal or pathological) or survival in esophageal cancer patients (stages II to IV) receiving oxaliplatin, 5-fluorouracil (5FU) and radiation, we measured in endoscopic primary tumor biopsies from 38 patients, the expression of seven genes (gammaGCS, gammaGT, MRP-2, ERCC-1, XPA, TS and DPD) prior to treatment, 1 week following oxaliplatin alone and at the end of the combined radio-chemotherapy cycle using real time QRT-PCR. A higher pretreatment level of XPA was related to shorter survival with a hazard ratio of 2.43 (90% confidence interval 1.09 to 5.43) using Cox regression modeling. However, multivariate analysis with a Cox model indicated low expression of XPA or TS and combined stages II and III had a higher probability of survival (for XPA: hazard ratio 3.0 and 90% C.I. of 1.3 to 6.9, with adjustment for stage included; for TS: hazard ratio is 1.98 with 90% C.I. of 0.94 to 4.20. The expression of TS, gammaGCS, ERCC-1 and MRP-2 declined from D 1 to the end of the cycle (p<0.05, sign test). A validation and further understanding of the findings need to be carried out in a larger study with a more homogeneous population of patients.
authors.affiliation: Aptium Oncology, Comprehensive Cancer Center of the Desert, Palm Springs, CA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Leichman
authors.forename: D
authors.initials: D
authors.lastname: Lawrence
authors.forename: C G
authors.initials: CG
authors.lastname: Leichman
authors.forename: H
authors.initials: H
authors.lastname: Nava
authors.forename: E
authors.initials: E
authors.lastname: Nava
authors.forename: G
authors.initials: G
authors.lastname: Proulx
authors.forename: K
authors.initials: K
authors.lastname: Clark
authors.forename: N I
authors.initials: NI
authors.lastname: Khushalani
authors.forename: J
authors.initials: J
authors.lastname: Berdzik
authors.forename: W
authors.initials: W
authors.lastname: Greco
authors.forename: P
authors.initials: P
authors.lastname: Smith
authors.forename: P J
authors.initials: PJ
authors.lastname: Creaven
authors.forename: J L
authors.initials: JL
authors.lastname: Kepner
authors.forename: M M
authors.initials: MM
authors.lastname: Javle
authors.forename: L
authors.initials: L
authors.lastname: Pendyala
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001706:Biopsy / Q000379:methods; D003131:Combined Modality Therapy; D016145:Endoscopy, Digestive System; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000532:radiotherapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007820:Laryngeal Mucosa / Q000187:drug effects / Q000378:metabolism; D008297:Male; D000089762:Multidrug Resistance-Associated Protein 2; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D000077150:Oxaliplatin; D011829:Radiation Dosage; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: C000715087:ABCC2 protein, human; D000089762:Multidrug Resistance-Associated Protein 2; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D005472:Fluorouracil