Apatinib Dose Titration in Advanced or Metastatic Gastric Cancer

Inclusion Criteria:

1. ≥ 18 and ≤ 70 years of age
2. Histological confirmed advanced or metastatic adenocarcinoma of the stomach
3. Have failed for at least 2 lines of chemotherapy
4. Life expectancy of at least 12 weeks
5. Eastern Cooperative Oncology Group Performance Status of 0 or 1
6. At least one measurable lesion beyond stomach (larger than 10 mm in diameter by spiral CT scan)
7. Duration from the last therapy is more than 6 weeks for nitroso or mitomycin
8. More than 4 weeks for operation or radiotherapy or cytotoxic agents
9. Adequate hepatic, renal, heart, and hematologic functions

Exclusion Criteria:

1. Pregnant or lactating women
2. History of other malignancies except cured basal cell carcinoma of skin and carcinoma in-situ of uterine cervix
3. Hypertension and unable to be controlled within normal level following treatment of anti-hypertension agents (systolic blood pressure \> 140 mmHg, diastolic blood pressure \> 90 mmHg)
4. Any factors that influence the usage of oral administration
5. Evidence of central nerves system metastasis
6. Intercurrence with one of the following: coronary artery disease, arrhythmia ,heart failure
7. proteinuria ≥ (+)
8. International Normalized Ratio \> 1.5 and activated partial thromboplastin time \> 1.5 × Upper limit of normal（ULN）
9. Certain possibility of gastric or intestine hemorrhage
10. Less than 4 weeks from the last clinical trial
11. Prior VEGFR inhibitor treatment
12. Disability of serious uncontrolled intercurrence infection Objective evidence of previous or current pulmonary fibrosis history, interstitial pneumonia, Pneumoconiosis, radiation pneumonitis, drug-related pneumonia, Pulmonary function damaged seriously etc