Phase III Study to Compare Perioperative Chemotherapy of Oxaliplatin Combined With S-1(SOX) Versus SOX or Oxaliplatin With Capecitabine (XELOX) as Post-operative Chemotherapy in Locally Advanced Gastric Adenocarcinoma With D2 Dissection

Peri-operative treatment of locally advanced gastric cancer (LAGC) has always been argued by eastern and western scholars. For patients with clinical stage of cT4b/N+M0, or cT4aN+M0, the prognosis is rather poor, and the primary lesions might not be resectable at the time of diagnosis. MAGIC study has showed that pre-and post-operative chemotherapy with 3 cycles of ECF has increased 13% on 5yOS compared with surgery alone; However, eastern studies such as ACTS GC or CLASSIC showed that TS-1 monotherapy or XELOX (oxaliplatin/capecitabine) combination given as adjuvant chemotherapy for stage II or III patients after D2 surgery could achieve the significant survival benefit. So whether perioperative or post operative therapy is more beneficial for LAGC patients lacks of data supported by prospective study.

So in this prospective randomized phase III study, the investigators aim to compare the survival benefit as well as the safety for SOX (oxaliplatin/TS-1) as perioperative therapy versus SOX or XELOX as postoperative therapy after D2 dissection.

detailed discription of protocol updated on Feb 2013; detailed discription of protocol updated on Apr 2013; detailed discription of protocol updated on Oct 2013;

Eligibility Criteria:
Inclusion Criteria:

* sign written informed consent form
* age ≥ 18 years
* pathologically confirmed gastric or GEJ adenocarcinoma
* disease at clinical stage of resectable or potentially resectable LAGC（T4a-b/N+M0）
* No prior antitumor treatment is allowed, including chemotherapy, radiotherapy, immune therapy or target therapy
* Adequate organ function as defined below:

Hematologic ANC ≥ 1.5\*109/l Hemoglobin ≥ 9 g/dl Platelets ≥ 100\*109/l Hepatic Albumin ≥ 30g/l Serum bilirubin ≤ 1.5×ULN AST and ALT ≤ 2.5×ULN ALP ≤ 2.5×ULN TBIL ≤ 1.5×ULN Renal Serum Creatinine \< 1.5 ULN

* KPS ≥ 70
* Adequate lung and heart function
* Negative serum or urine pregnant test within 7 days prior to randomization for child-bearing age women
* Sexually active males or females willing to practice contraception during the study until 30 days after end of study.

Exclusion Criteria:

* Refuse to provide blood/tissue sample；
* With distant metastasis；
* Sexually active males or females refuse to practice contraception during the study until 30 days after end of study.
* Known hypersensitivity reaction or metabolic disorder to fluorpyrimidines or oxaliplatin；
* ≥ grade 1 peripheral neuropathy；
* History of organ transplantation（including autologous bone marrow transplantation and Peripheral stem cell transplantation）；
* Prior long term steroid therapy (excluding short term steroid treatment which is completed prior to \> 2 weeks of study enrollment)；
* Patients with central nervous system(CNS) disorder or peripheral nervous system disorder or psychiatric disease；
* Concurrent severe infection；
* unable to swallow; (complete or incomplete)gastrointestinal obstruction; gastrointestinal bleeding; gastrointestinal perforation；
* Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical disorder that would interfere with the subject's safety (including current active hepatic, biliary, renal, respiratory disease, uncontrolled diabetes hypertension et al)；
* History of other malignancy. However, subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma, are eligible；
* Known history of uncontrolled or symptomatic angina, uncontrolled arrhythmias and hypertension, or congestive heart failure, or cardiac infarction within 6 months prior to study enrollment, or cardiac insufficiency；
* Person with no capacity (legally) or inappropriate to continue study treatment for ethics/medical reasons；