Apatinib Combined With S-1 as Maintenance Therapy for HER-2 Negatived Gastric Cancer

Inclusion Criteria:

1. Histologically proved advanced HER-2 negatived gastric adenocarcinoma;
2. At least a unresectable factor before operation via CT, MRI, or PET-CT: difficult resection of locally advanced gastric cancer(T4b); hepatic metastasis (H1; at most five lesions, total diameter ≤8 cm); Peritoneal metastasis(CY1, P1) ; Definitely diagnosed as unresectable GC via exploratory laparoscopy or laparotomy;
3. ECOG performance status 0-2;
4. Age≥ 18 years old, Life expectancy estimated than 3 months;

5. For results of blood routine test and biochemical tests:

   Hgb ≥ 80g/L, WBC ≥ 4000/mm3, ANC ≥ 1.5×109/L, platelets ≥ 80×109/L ALT and AST ≤ 2.5 x upper normal limit (UNL), and ≤ 5 x UNL（Hematogenous metastases）, Serum Total bilirubin ≤ 1.5 X UNL, Serum Creatine ≤ 1.5 x UNL ；

6. Good cardiac function before the recruitment, no seizure of myocardial infarction in past half years, and controllable hypertension and other coronary heart disease;
7. Not concomitant with other uncontrollable benign disease before the recruitment(e.g. the infection in the kidney, lung and liver);
8. Informed consent.

Exclusion Criteria:

1. Subjects with poor-controlled arterial hypertension (systolic blood pressure> 140 mmHg and diastolic blood pressure > 90 mm Hg) despite standard medical management;
2. Coronary heart disease greater than Class I; I-level arrhythmia (including QT interval prolongation, for man ≥ 450 ms, for woman ≥ 470 ms) together with Class I cardiac dysfunction;
3. Patients with positive urinary protein;
4. Factors that could have an effect on oral medication (such as inability to swallow, chronic diarrhea and intestinal obstruction);
5. Subjects with high gastrointestinal bleeding risk, including the following conditions: local active ulcer lesions with positive fecal occult blood test (++); history of black stool, or vomiting blood in the past 2 months;
6. Contraindications include allergy to apatinib and/or its accessories, active bleeding, intestinal perforation, intestinal obstruction, within 30 days after surgery, drugs with poor-controlled hypertension, Class Ⅲ-Ⅳ cardiac dysfunction （NYHA standard）, severe hepatic and renal dysfunction（level 4）if apatinib use is considered;
7. Abnormal Coagulation (INR>1.5, APTT>1.5 UNL), with tendency of bleed;
8. Pregnant or lactating women; Any other condition that might place the patient at undue risk or preclude a patient from completing the study;
9. Treated with 4 cycles chemotherapy included Tegafur;
10. Other conditions regimented at investigators' discretion.