Primary Outcome Measures:
- Pathologic complete response rate [ Designated as safety issue: No ]
- Frequency and severity of toxicity [ Designated as safety issue: Yes ]
- Correlation of DNA repair genes, target enzymes, and angiogenic factors with response, progression-free survival (PFS), and overall survival (OS) [ Designated as safety issue: No ]
- Correlation of haplotypes of candidate genes of TS, TP, ERCC-1, XPD, GST-P1, cyclooxygenase-2, EGF receptor, TGF-β, VEGF, and IL-8 with response, toxicity, PFS, and OS [ Designated as safety issue: Yes ]
- Feasibility of performing comparative genomic hybridization for analysis of DNA copy number changes in predicting response [ Designated as safety issue: No ]
OBJECTIVES:
- Determine the pathologic complete response rate in patients with primary gastric adenocarcinoma treated with neoadjuvant chemoradiotherapy comprising oxaliplatin, capecitabine, and radiotherapy.
- Assess the frequency and severity of toxicities associated with this regimen.
- Explore, preliminarily, the association between DNA repair genes (ERCC-1, XRCC1, GST-P1, XPD, XPA, ribonucleotide reductase), target enzymes (thymidylate synthase [TS], dihydropyrimide dehydrogenase, thymidine phosphorylase [TP]), and angiogenic factors (vascular endothelial growth factor [VEGF], epidermal growth factor [EGF], PD-ECGF, basic fibroblast growth factor, TSP-1 and -2, transforming growth factor [TGF]-β, and IL-8) and response to neoadjuvant therapy in patients with adenocarcinoma of the stomach.
- Explore, preliminarily, the association of haplotypes of candidate genes of TS, TP, ERCC-1, XPD, GST-P1, cyclooxygenase-2, EGF receptor, TGF-β, VEGF, and IL-8 with response and toxicity to neoadjuvant chemoradiation therapy in these patients.
- Explore, preliminarily, the feasibility of performing comparative genomic hybridization for analysis of DNA copy number changes in predicting response to neoadjuvant chemoradiation therapy.
OUTLINE: This is a multicenter, pilot study.
- Neoadjuvant chemotherapy: Patients receive oxaliplatin IV over 2 hours on days 1 and 22 and oral capecitabine twice daily on days 1-14 and 22-35 in the absence of disease progression or unacceptable toxicity.
- Neoadjuvant chemoradiotherapy: Patients receive oral capecitabine twice daily on days 43-77 and undergo radiotherapy once daily on days 43-47, 50-54, 57-61, 64-68, and 71-75 in the absence of disease progression or unacceptable toxicity.
- Surgery: Patients with stable or responding disease undergo surgery 4-6 weeks after completion of chemoradiotherapy.
Tumor tissue is obtained at surgery or endoscopic biopsy. Gene expression analysis and comparative genomic hybridization testing are conducted on the tissue. Blood is drawn prior to beginning study treatment and is analyzed for germline polymorphisms.
After completion of study treatment, patients are followed periodically for up to 3 years.
PROJECTED ACCRUAL: A total of 75 patients will be accrued for this study.