Apatinib Dose Titration in Advanced or Metastatic Gastric Cancer

Inclusion criteria

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

Exclusion criteria

• Pregnant or lactating women
• History of other malignancies except cured basal cell carcinoma of skin and carcinoma in-situ of uterine cervix
• 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)
• Any factors that influence the usage of oral administration
• Evidence of central nerves system metastasis
• Intercurrence with one of the following: coronary artery disease, arrhythmia ,heart failure
• proteinuria ≥ (+)
• International Normalized Ratio > 1.5 and activated partial thromboplastin time > 1.5 × Upper limit of normal（ULN）
• Certain possibility of gastric or intestine hemorrhage
• Less than 4 weeks from the last clinical trial
• Prior VEGFR inhibitor treatment
• 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