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: L Leichman, D Lawrence, C G Leichman, H Nava, E Nava, G Proulx, K Clark, N I Khushalani, J Berdzik, W Greco, P Smith, P J Creaven, J L Kepner, M M Javle, L Pendyala
• Journal: Journal of chemotherapy (Florence, Italy) (J Chemother) Vol. 18 Issue 5 Pg. 514-24 (Oct 2006) ISSN: 1120-009X [Print] England
• PMID: 17127229 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

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

Topics

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