Apatinib with Oxaliplatin and S-1 Treatment for Advanced Hepatoid Adenocarcinoma of the Stomach

Inclusion Criteria:

1. Age: 18 to 70 years old, no gender limitation;
2. Histopathological diagnosis of locally advanced, recurrent or metastatic HAS (pathological histomorphology and immunohistochemical diagnosis of AFP, sal-like 4(SALL4), Hep, glypican-3(GPC3), etc.);
3. Immunohistochemical(IHC) human epidermal growth factor receptor-2 (HER2) negative persons; HER2 positive is defined as IHC 3+ or IHC 2+ and fluorescence in situ hybridization(FISH)+, and FISH positive is defined as the ratio of HER2 gene copy number to chromosome 17 centromere(CEP17) signal number ≥2.0;
4. According to the RECIST 1.1 standard, at least one measurable lesion (spiral CT scan ≥10mm);
5. ECOG performance status(PS): 0-2 points;
6. The expected survival time is ≥3 months;
7. The main organs are functionally normal, without serious blood, heart, lung, liver, kidney dysfunction and immune deficiency disease. The blood test meets the following requirements; (1) Routine blood examination, which must be met (no blood transfusion within 14 days);

   1. HGB≥100g/L;
   2. WBC≥4.0×10\^9/L; absolute neutrophil count(ANC) ≥2.0×10\^9/L;
   3. PLT≥2.0×10\^9/L; (2) The biochemical inspection must meet the following standards:

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   1. BIL≤1.5 times the upper limit of normal (ULN);
   2. Alanine aminotransferase(ALT) and aspartate aminotransferase(AST)≤2.5×ULN; if there is liver metastasis, ALT and AST≤5×ULN;
   3. serum Cr≤1.5×ULN, endogenous creatinine clearance≥50ml/min (Cockcroft-Gault formula); (3) Occult blood in stool (-); (4) Urine routine is normal, or urine protein \<(++), or 24-hour urine protein \<1.0g;
8. The coagulation function is normal, without active bleeding and thrombosis disease;

   1. International standardized ratio INR≤1.5×ULN;
   2. Partial thromboplastin time APTT≤1.5×ULN;
   3. Prothrombin time PT≤1.5×ULN;
9. Female subjects with fertility and male subjects whose partner is a female of childbearing age who need to take effective contraceptive measures during the study treatment period and at least 6 months after the last use of the study drug;
10. Subjects voluntarily participate in this study and sign an informed consent form (ICF);
11. Those who have good compliance and can follow up as required by the plan.

Exclusion Criteria:

1. Various types of liver inflammatory diseases (especially hepatitis A, B, and C viral hepatitis active period) and other diseases that may produce AFP such as liver cirrhosis;
2. Germ cell tumors;
3. Have previously received any regimen of palliative chemotherapy for gastric cancer;
4. Have previously received apatinib treatment;
5. S-1 and/or oxaliplatin have been used in the past 6 months;
6. Those who have hypertension and cannot be reduced to the normal range after treatment with antihypertensive drugs (shrinking Pressure\>140mmHg or diastolic pressure\>90mmHg);
7. Suffering from coronary heart disease ≥2 grade, arrhythmia corrected QT interval(QTc) interval prolonged male\> 450ms, female;\>470ms) and cardiac insufficiency;
8. There are many factors that affect the absorption of oral drugs (such as inability to swallow, nausea and vomiting, chronic abdominal Diarrhea and intestinal obstruction, etc.);
9. Patients at risk of gastrointestinal bleeding or those with a history of gastrointestinal bleeding within 1 month;
10. Abnormal blood coagulation function (INR\>1.5×ULN, activated partial thromboplastin time(APTT)\>1.5×ULN), those with bleeding tendency;
11. Those with thrombotic diseases or receiving anticoagulant treatment;
12. Those with peripheral sensitive neuropathy with dysfunction;
13. Central nervous system metastasis;
14. Pregnant or lactating women;
15. Those who have participated in other clinical research in the past 30 days;
16. Other patients considered by the treating physician to be unsuitable for inclusion