The purpose of this study is to evaluate the effectiveness and safety of S-1+Oxaliplatin vs.S-1+Cisplatin First-line Treatment in Advanced or Recurrent Non-intestinal Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma Patients.

The primary endpoint is Overall survival time (OS).Secondary endpoints are overall response rate (ORR), time to treatment failure (TTF),progression free survival (PFS)and the adverse reactions(AE) of the two groups .

Study design:

This is a prospective randomized control study.

Sample size:

Sample size considerations were based on the survival end point. The improvement in median survival from 10 months in the S-1+cisplatin arm to 13 months in the S-1+oxaliplatin arm was considered clinically relevant in this patient population. A total of 576 patients were required for a two-tailed log-rank test at the 5% significance and at least 80% power. The planned enrolled time was 48 months and 1 year of follow up, and a drop-out rate of 5%.

Inclusion Criteria:

1. histologically confirmed unresectable advanced or recurrent diffuse-type or mixed-type gastric adenocarcinoma or gastroesophageal junction adenocarcinoma.

2. 18 years old to 75 years old, able to conduct oral administration.

3. Measurable disease or non-measurable but evaluable disease, according to the Response Evaluation Criteria in Solid Tumours(RECIST 1.1)

4. No palliative chemotherapy and radiotherapy. Previous adjuvant or neoadjuvant chemotherapy , if applicable, more than 12 months.

5. ECOG systemic status score of 0 to 2.

6. normal organ function, that meet the following criteria:

   1. ALT and AST(≤2.5 times ULN (≤5 times ULN in patients with liver metastases)
   2. ALP ≤ 2 times ULN ; (for patients with liver metastases can be no limit to the ALP).
   3. Total bilirubin ≤ 1 times ULN.
   4. Absolute neutrophil count ≥ 2.0 × 10^9 / L.
   5. Platelet count ≥ 100 × 10^9 / L.
   6. Hemoglobin ≥ 80g / L.
   7. Creatinine ≤ 1.25 times ULN.
   8. The estimated creatinine clearance ≥ 60 mL/min (Cockcroft-Gault formula).

7. Signed informed consent, treatment, follow-up and inspection in accordance with the study protocol.

8. Life expectancy greater than 3 months.

9. At least 3 weeks after major surgery.

Exclusion Criteria:

1. Previous adjuvant or neoadjuvant chemotherapy within the prescribed time

2. the investigator determines that the patient is not suitable for participation in this study, and specifically includes (but is not limited to):

   1. The past five years there have been other malignancies, but after appropriate treatment of cervical carcinoma in situ and non-melanoma skin cancer.
   2. brain metastases or leptomeningeal metastasis.
   3. myocardial infarction (within the past six months), severe unstable angina, congestive heart failure.
   4. Serious complications (including paralytic ileus, intestinal obstruction, interstitial pneumonia, lung fibrosis, beyond the control of diabetes, renal insufficiency and cirrhosis of the liver, etc.).
   5. Chronic nausea, vomiting, or diarrhea (per day greater than or equal to 4 times or watery stools).
   6. Gastrointestinal bleeding, and need for frequent blood transfusions.
   7. human immunodeficiency virus (HIV) carrier or suffering from AIDS (AIDS).
   8. Suffering from a mental illness.
   9. neuropathy severity ≥grade 2 .
   10. Infectious disease or inflammation, body temperature ≥ 38 ℃.

3. Cisplatin, oxaliplatin, or S-1 allergy.

4. Pregnancy or breast-feeding women.

5. refused to take appropriate contraceptive measures (including male patients).

6. Under experimental drug within 4 weeks.

7. Under other anti-cancer treatment.

8. HER2 IHC(3+) or IHC(2+) /FISH(+)