title: Controlling angiogenesis in gastric cancer: A systematic review of anti-angiogenic trials.
abstract: Angiogenesis is a promising therapeutic target to inhibit tumor growth. This review summarizes data from clinical trials of anti-angiogenic agents in gastric cancer.
  
  
  
  A systematic search of PubMed, Embase and conference databases is performed to identify clinical trials with specific anti-angiogenic agents in gastric cancer treatment
  
  
  
  The risk of disease progression (37-52%) and death (19-22%) with ramucirumab as second-line treatment decreases in phase III trials in advanced gastric cancer. No significant improvement in overall survival (OS) with the addition of bevacizumab to chemotherapy is shown. Bevacizumab or ramucirumab combined with traditional chemotherapy is associated with higher adverse event rate compared to chemotherapy alone. Except for apatinib, phase II trials of other tyrosine kinase inhibitors (TKIs) may improve overall response rate, but there are no significant improvements in OS and progression-free survival (PFS) when combined with chemotherapy.
  
  
  
  Phase III trials in advanced gastric cancer have demonstrated improved outcome with ramucirumab as second-line treatment. Most of the other studies on anti-angiogenic agents in gastric cancer have reported improvement in response rate but not in OS compared to chemotherapy alone. Future research is expected in optimizing the anti-angiogenic therapy combined with traditional treatment.
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Shan
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Rulin
authors.initials: R
authors.lastname: Miao
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Kan
authors.initials: K
authors.lastname: Xue
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Zhemin
authors.initials: Z
authors.lastname: Li
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Ziyu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Zhaode
authors.initials: Z
authors.lastname: Bu
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Aiwen
authors.initials: A
authors.lastname: Wu
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Lianhai
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Xiaojiang
authors.initials: X
authors.lastname: Wu
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Xianglong
authors.initials: X
authors.lastname: Zong
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Shuangxi
authors.initials: S
authors.lastname: Li
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Ji
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Ziyu
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Ziran
authors.initials: Z
authors.lastname: Li
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, China. Electronic address: jiafuj@hotmail.com.
authors.forename: Jiafu
authors.initials: J
authors.lastname: Ji
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D058990:Molecular Targeted Therapy; D009389:Neovascularization, Pathologic; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000098:blood supply* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016896:Treatment Outcome; D059016:Tumor Microenvironment
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D047428:Protein Kinase Inhibitors
keywords: Angiogenesis inhibitors; Antineoplastic agents; Antineoplastic combined chemotherapy protocols; Controlled clinical trial; Gastric neoplasms; Vascular endothelial growth factor antagonists and inhibitors