Genotype Guided Chemotherapy in Gastric Cancer Patients

In gastric cancer patients treated with 5-FU and cisplatin, higher tumor TS levels were associated with a less favorable response (29% vs. 68%; p=0.024). Similarly, in a study in which patients were treated with high dose 5-FU, patients with high TS expression had a response rate of only 12.5%. Conversely a response rate of 92.9% was observed in patients with low tumor TS expression. A longer but not statistically significant survival advantage was observed in patients with the TSER\*2 allele compared with the TSER\*3/\*3 patients. Additionally, a review by Patel et al. identified approximately 20 gastric cancer studies that have found a positive association between TSER genotype and clinical response (in either direction). Therefore, the primary goal of this proposal is to prospectively genotype patients, select patients with "good risk" TSER genotypes (TSER\*2\*/\*2 or \*2/\*3) and treat them with a standard 5-FU containing regimen (FOLFOX) in order to improve clinical outcomes, while randomize patients with the "poor risk" TSER genotype (\*3/\*3) to either the standard 5-FU containing regimen or another non-5-FU-based regimen (docetaxel/cisplatin).