Application of Two Anti-angiogenesis Drugs Combined With Chemotherapy in Advanced Colorectal Cancer Under the Background of Precision Medical

The purpose of this study is to determine whether Endostar pumping into vein with Thalidomide are more effective in the treatment of Advanced Colorectal Cancer (ACRC).

Endostar have anti-tumor activity by against vascular endothelial growth factor.

Thalidomide is a therapeutic for insomnia and vomiting. It is also used for tumor treatment as an Anti-angiogenesis drug and immune regulator in recently years.

1. Evaluated the therapeutic effects and survival benefits of ACRC treatment by using the Endostar and Thalidomide combined with XELOX regimens. (including the RR, DCR, PFS, and QOL);
2. Evaluated the security and tolerance by treating with Endostar and Thalidomide (the occurrence of adverse reaction, the degree, the regularity and control measures, etc.);
3. Detected the histological markers (VEGF/VEGFR, PDGF/PDGFR, BFGF/FGFR, cox-2, Her-2, K-Ras and p53) before the patients into the group. Make a retrospective analysis of individual molecules indicators to guide significant therapy of ACRC.

Eligibility Criteria:
Inclusion Criteria:

1. The patients with stage IV colorectal cancer can't receive operative treatment diagnosed by Histopathological or cytological examination or can receive operation after conversion therapy.
2. The niave patients relapse and metastasize after more than 6 months' chemotherapeutic diapause after operation or adjuvant chemotherapy or refuse to another operate or need operate only after conversion therapy
3. Have at least one measurable nidus, Ordinary CT or MRI scan nidus 20 mm or higher, Spiral CT and PET - CT scan nidus 10 mm or higher.
4. The first 3 weeks before entering the group have stopped chemotherapy or radiotherapy and recovered from previous treatment of toxic effects. The patients who have received the treatment of delayed toxicity drugs (such as mitomycin or nitrourea) should stop treatment of 6 weeks;
5. ECOG score of 0 to 2 points.
6. Expected survival period for 3 months or more.
7. Aged 18 to 75 years of age, and gender not limited.
8. The electrocardiogram is normal and the body doesn't have unhealed wounds.
9. Peripheral blood cell count, WBC 4.0 x 109 / L or higher, PLT 80 x 109 / L or higher, Hb 90 g/L or higher.
10. Renal function, Cr 2.0 x UNL (upper limit of normal) or less.
11. Liver function, AST, ALT were 2.5 times the normal limit or less (if identified as liver metastasis, five times the normal limit or less).
12. Previous have no severe allergic reactions on biological agents, especially e. coli genetically engineered products.
13. Voluntary to participate in groups, good compliance, willing to cooperate with test observation and sign a written informed consent.

Exclusion Criteria:

1. Pregnant, lactating women,or female patient who have fertility ability but have not taken contraceptive measures;
2. Patients who exist serious acute infection and have not been controlled；or patients who exist purulent infection,chronic infection and delayed wound healing;
3. Patients with serious heart disease, including:congestive heart failure ,uncontrollable high-risk arrhythmias,unstable angina, myocardial infarction, severe heart valve disease and resistant hypertension;
4. Patients whose target lesions had previously received radiation therapy or other topical treatment(radio frequency, ultrasonic, freezing);
5. Patients who suffered from uncontrollable neurological and psychiatric diseases or mental disorders, have poor compliance as well as can not cope with others and failed to narrative therapy respond;patients whose primary brain or central nervous system metastases disease had not been controlled and those with Cranial hypertension or neuropsychiatric symptoms;
6. Patients who had meanwhile participated in other clinical trials;
7. Other circumstances which researchers considered that patients should not participate in this test.