Updated results of an exploratory gene expression analysis for primary esophageal cancer (PEC) patients (pts) treated with oxaliplatin (OXP), protracted infusion (PI) 5FU and radiation (XRT)

Abstract

4014 Background: In a study designed to explore the relationship between expression of TS, γGCS, γGT, ERCC-1 and XPA genes and clinical outcome for 38 pts with PEC, who received OXP (85 mg/m2 day (D)1, D15 and D29), PI 5FU (180 mg/m2 D8-D42 ) and XRT (5040 cGy beginning D8 for 28 fractions) TS appeared to be prognostic for survival (Leichman et al., Proc. ASCO, 22:263, 2003). Because recurrence and deaths have continued, an updated analysis for pts followed through October 2003 is presented including expression of DPD and MRP-2 genes. Methods: Pts had endoscopic biopsies of PEC prior to OXP (D1), prior to 5FU and XRT (D8) and at the end of treatment (ET). Gene expression was assayed typically in 2 specimens at each time point in 29 (ET) to 37 (D1) pts by real time QRT-PCR and expressed relative to β-actin. The mean mRNA levels at each time were logarithmically transformed and using Cox proportional hazards model with time-dependent covariates explored for relationships to survival (S) and progression free survival (PFS). Results: Overall median S (n=38) and PFS (n=38) are 26.9 and 12.1 months (mo) respectively at a median follow-up of 31 and 30 mo for the censored pts. Stage 4 (n=22) versus Stages 2/3 (n=16) showed no differences in S (90% C.I. on hazard ratio: 0.9, 3.8) or PFS (90% C.I. on hazard ratio: 0.9, 3.2). Now, a year after our initial analysis, only D1 mean XPA expression showed relation to S in a model that included stage (XPA 90% C.I. on hazard ratio: 1.3, 6.9). XPA as a time-dependent covariate at D1, D8 and ET for 28 pts with stage included also showed a relation to S (90% C.I. on hazard ratio: 1.0, 7.5). None of the biomarkers on D1 or as time-dependent covariates showed a relation to PFS. Conclusions: In successive exploratory analyses of PEC pts treated with OXP, 5FU and XRT, TS and XPA, gene expressions demonstrated variable time dependent relationships to survival. Expression of these genes, and their association with survival for PEC pts undergoing multimodality are appropriate for further larger studies. (Supported by CA 915490 and CA 16056) Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sanofi-Synthalabo