Inclusion Criteria:

1. histologically or cytologically confirmed pancreatic adenocarcinoma that was not
amenable to potentially curative surgery.

2. All patients must have developed progressive disease (PD) while receiving or within 6
months after discontinuing palliative gemcitabine-based chemotherapy

3. Prior radiation therapy was allowed provided that the only sites of measurable
disease were not located within the radiation port.

4. 18 years of age or older

5. Karnofsky performance status (KPS) of 60-100 points

6. measurable disease as defined by Response Evaluation Criteria in Solid Tumors
(RECIST) criteria

7. Adequate hematologic, renal, and hepatic function was required as deWned by the
following: WBC ≥3.5×109/L, absolute neutrophil count ≥ 1.5 × 109/L, platelet count
≥100 × 109/L, hemoglobin≥9g/dL, total bilirubin ≤2.5 upper limit of normal
[ULN],AST≤2.5 ULN, or≤5 ULN if there was evidence of liver metastases;alkaline
phosphatase≤ 2.5 ULN, or≤ 5 ULN if there was evidence of liver Metastases creatinine
clearance≤50 mL/min,

8. life expectancy of at least 12 weeks

Exclusion Criteria:

1. patients had clinically apparent CNS metastases or carcinomatous meningitis

2. another active malignancy, or any history of other malignancy within the past 5 years
except for nonmelanoma skin cancer and carcinoma in situ of the cervix

3. more than 3 weeks intervals between the last administration of the prior chemotherapy
regimen and study entry

4. more than 4 weeks intervals between the last administration of the targeted therapy
regimen and study entry

5. major surgery within the prior 6 weeks;

6. Pregnant or lactating women

7. tumor involvement of major blood vessels

8. uncontrolled intercurrent illness

9. A history of myocardial infarction or stroke within the last 6 months, uncontrolled
hypertension, unstable angina

10. clinically significant cardiac disease (eg, congestive heart failure, symptomatic
coronary artery disease and cardiac arrhythmias not well controlled with medication,
or myocardial infarction)

11. urine protein ≥ 500 mg in 24 hours;

12. evidence of bleeding diathesis or coagulopathy

13. Patients on therapeutic doses of low-molecular weight heparin

14. Patients who received thrombolytic agents within the previous month or who required
full-dose anticoagulation.