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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
330
TS gene will be genotyped for each patients prior to chemotherapy. Patients will be assigned to different arms according to specific TSER genotype.
Institute of Clinical Pharmacology
Changsha, Hunan, China
disease control rate
Determine whether the disease control rate (DCR) at 6 and 12 weeks in TSER\*3/\*3 patients with metastatic gastric cancer will be increased by using a non fluoropyrimidine containing regimen compared to fluoropyrimidine-containing regimens.
Time frame: 6 and 12 weeks after the first chemotherapy
time to progression
TTP is defined in this study as: "The length of time from the date of the start of treatment for gastric cancer until the disease starts to get worse or spread to other parts of the body."
Time frame: 2 years maximum
median overall survival
median overall survival is defined in this study as: "The length of time from the start of treatment for a disease that half of the patients in a group of patients diagnosed with the disease are still alive."
Time frame: 2 years maximum
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