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

J Chemother. 2006 Oct;18(5):514-24. doi: 10.1179/joc.2006.18.5.514.

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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biopsy / methods
  • Combined Modality Therapy
  • Endoscopy, Digestive System
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / radiotherapy
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / pharmacology*
  • Gene Expression / drug effects
  • Humans
  • Laryngeal Mucosa / drug effects
  • Laryngeal Mucosa / metabolism
  • Male
  • Multidrug Resistance-Associated Protein 2
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / pharmacology*
  • Oxaliplatin
  • Radiation Dosage
  • Survival Analysis
  • Treatment Outcome

Substances

  • ABCC2 protein, human
  • Multidrug Resistance-Associated Protein 2
  • Organoplatinum Compounds
  • Oxaliplatin
  • Fluorouracil