Anti-HER2 Therapy in Patients of HER2 Positive Metastatic Carcinoma of Digestive System

Inclusion Criteria: * Signed informed consent. * Male and female patients aged from 18 to 75 years * Histologically confirmed Colorectal cancer,Esophagus squamous cell carcinoma, biliary tract cancer, and digestive system tumor beyond CRC and GC\&GEJA with the following specifications: * genetic testing conformed KRAS/NRAS/BRAF all wild type for colorectal cancer * Detection of a carcinoma with HER2 3+ (IHC) or HER2 2+ (IHC) with amplification proven by fluorescence in situ hybridization(FISH), silver in situ hybridization（SISH） or chromogenic in situ hybridization（CISH） using gastric cancer criteria by an accredited local pathologist. * Relapse or metastatic diseases, at least one measurable lesion according to RECIST 1.1, anticipated survival ≥ 12 weeks. * ECOG Performance status 0-1. * Patients who failed at least first line systemic therapy. * Adequate organ function as determined by the following laboratory results: * Absolute neutrophil count ≥1500 cells/mm3, * Platelet count ≥ 90,000 cells/mm3, * Hemoglobin ≥9.0 g/dL * Total bilirubin ≤ 1.5 upper limit of normal (ULN). * serum glutamate oxaloacetate transaminase(SGOT,AST), serum glutamate pyruvate transaminase(SGPT,ALT) \< 2.5 ULN without liver metastases; \< 5 ULN with liver metastases. * serum creatinine \< 1.5 * ULN OR creatinine clearance ≥ 40 mL/ min. * If able to reproduce, patients must be willing to use highly effective methods of contraception during treatment and for 7 months after the end of treatment. Exclusion Criteria: * Known hypersensitivity against treatment regimen. * Baseline left ventricular ejection fraction(LVEF) \< 50% (measured by echocardiography or MUGA). * Previous anti-her treatment. * Immune therapy, biological therapy or any participation in clinical trial in previous two weeks. * Surgery and not recovered in previous three weeks * Clinical evidence of brain metastases, or uncontrolled epilepsy. * Serious uncontrolled systemic intercurrent illness, e.g. infections or poorly controlled diabetes. * Other malignancy within the last 5 years, except for carcinoma in situ of the cervix, or basal cell carcinoma. * Clinically significant active coronary heart disease, cardiomyopathy or congestive heart failure, New York Heart Association(NYHA) III-IV; poorly controlled hypertension (systolic BP \> 180 mmHg or diastolic BP \> 100 mmHg); clinically significant valvular heart disease; unstable angina pectoris, myocardial infarction or high risk uncontrollable arrhythmias. * Long term or high dose corticosteroids administration ( inhalation or short term oral administration for antiemesis and orexigenic is allowed) * Patients of legally incapacity or of medical and ethical reasons not fit for study. * Pregnant or lactating, or intending to become pregnant during the study. * Jaundice, ascites, and / or alkaline phosphatase ≥3 × ULN; and / or ≥3 grade (CTC-AE) of persistent proteinuria, urinary protein / creatinine ratio\> 3.5g / 24 hours or renal failure need blood or peritoneal dialysis. * Presence of \> grade 2(CTC-AE) persistent infection; unhealed wounds, ulcer or fracture, or patients with a history of organ transplant. * Evidence of coagulation disorders. Like presence ≥grade 3 (CTC-AE) bleeding events. * Known HIV or hepatitis B virus(HBV), hepatitis C virus(HCV) infection. * Any \> grade 1 unresolved toxicity due to previous treatment (CTC-AE), except for alopecia, anemia and hypothyroidism). * Not suitable for the study evaluated by investigators * Known dihydropyrimidine dehydrogenase (DPD) deficiency. * History of exposure to the following cumulative doses of anthracyclines: * Doxorubicin \> 500 mg/m2 OR Epirubicin \> 720 mg/m2. * If another anthracycline or more than one anthracycline has been used, then the cumulative dose must not exceed the equivalent of 500 mg/m2 doxorubicin.