title: Apatinib for chemotherapy-refractory advanced metastatic gastric cancer: results from a randomized, placebo-controlled, parallel-arm, phase II trial.
abstract: OBJECTIVE
  Patients with metastatic gastric cancer (mGC) who do not respond to or who experience progression with second-line chemotherapy have no treatment options that clearly confer a survival benefit. This trial investigated the safety and efficacy of apatinib, an inhibitor of vascular endothelial growth factor receptor, as a treatment option for heavily pretreated patients with mGC.
  
  
  METHODS
  Patients who experienced treatment failure with at least two chemotherapeutic regimens were randomly assigned to receive placebo (group A), apatinib 850 mg once daily (group B), or apatinib 425 mg twice daily (group C).
  
  
  RESULTS
  We enrolled 144 patients onto this study. In groups A, B, and C, the median overall survival (OS) times were 2.50 months (95% CI, 1.87 to 3.70 months), 4.83 months (95% CI, 4.03 to 5.97 months), and 4.27 months (95% CI, 3.83 to 4.77 months), respectively, and the median progression-free survival (PFS) times were 1.40 months (95% CI, 1.20 to 1.83 months), 3.67 months (95% CI, 2.17 to 6.80 months), and 3.20 months (95% CI, 2.37 to 4.53 months), respectively. There were statistically significant differences between the apatinib and placebo groups for both PFS (P < .001) and OS (P < .001 and P = .0017). Nine patients had a partial response (three patients in group B and six patients in group C). Toxicities were tolerable or could be clinically managed. The most common grade 3 to 4 adverse events were hand-foot syndrome and hypertension. Hematologic toxicities were moderate, and grade 3 to 4 hematologic toxicities were rare.
  
  
  CONCLUSIONS
  Apatinib showed improved PFS and OS in heavily pretreated patients with mGC who had experienced treatment failure with two or more chemotherapy regimens.
authors.affiliation: Jin Li, Weijian Guo, Xiaodong Zhu, Dongmei Ji, and Xin Liu, Shanghai Cancer Center and Shanghai Medical College, Fudan University; Liwei Wang, Shanghai First People's Hospital; Leizhen Zheng, XinHua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai; Shukui Qin, The 81 Hospital of PLA, Nanjing; Hao Yu, School of Public Health, Nanjing Medical University, Nanjing; Jianming Xu, The 307 Hospital of the Academy of Military Medical Sciences, Beijing; Jianping Xiong, The First Affiliated Hospital of Nanchang University, Nanchang; Yuxian Bai, The Third Affiliated Hospital of Harbin Medical University, Harbin; Guoping Sun, The First Affiliated Hospital of Anhui Medical University, Hefei; Yan Yang, Gansu Cancer Hospital, Lanzhou; Nong Xu, The First Affiliated Hospital of Zhejiang University, Hangzhou; Ying Cheng, Jilin Cancer Hospital, Changchun; Zhehai Wang, Shandong Cancer Hospital, Jinan; and Min Tao, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.forename: Shukui
authors.initials: S
authors.lastname: Qin
authors.forename: Jianming
authors.initials: J
authors.lastname: Xu
authors.forename: Weijian
authors.initials: W
authors.lastname: Guo
authors.forename: Jianping
authors.initials: J
authors.lastname: Xiong
authors.forename: Yuxian
authors.initials: Y
authors.lastname: Bai
authors.forename: Guoping
authors.initials: G
authors.lastname: Sun
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.forename: Liwei
authors.initials: L
authors.lastname: Wang
authors.forename: Nong
authors.initials: N
authors.lastname: Xu
authors.forename: Ying
authors.initials: Y
authors.lastname: Cheng
authors.forename: Zhehai
authors.initials: Z
authors.lastname: Wang
authors.forename: Leizhen
authors.initials: L
authors.lastname: Zheng
authors.forename: Min
authors.initials: M
authors.lastname: Tao
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhu
authors.forename: Dongmei
authors.initials: D
authors.lastname: Ji
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Hao
authors.initials: H
authors.lastname: Yu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007390:International Agencies; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality; D009367:Neoplasm Staging; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D011379:Prognosis; D011725:Pyridines / Q000627:therapeutic use*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D055815:Young Adult
chemical_list: D011725:Pyridines; C553458:apatinib