title: Effects of single nucleotide polymorphisms on treatment outcomes and toxicity in patients treated with sunitinib.
abstract: OBJECTIVE
  We analyzed the efficacy and toxicity profile of sunitinib according to single nucleotide polymorphisms (SNPs) of vascular endothelial growth factor receptor (VEGFR) and Kinase insert domain receptor (KDR).
  
  
  METHODS
  We examined eight known SNPs of VEGFA and five SNPs of KDR among patients with gastric or biliary tract cancer who were treated with sunitinib. We retrospectively assessed clinical outcomes and their relationships to these SNPs.
  
  
  RESULTS
  A total of 63 patients were evaluable. Among candidate SNPs, rs2010963 and rs833068 of VEGFA, and rs1870377 of KDR were associated with poor time to treatment failure (TTF) (p=0.009, 0.002, and 0.029, respectively), while rs1870377 and rs7692791 of KDR were associated with poor overal survival (OS) (p=0.001 and 0.03, respectively). Multivariate analysis showed that only rs1870377 had significant effects on both TTF and OS. Toxicity evaluation indicated that rs1531289 of KDR was associated with grade 3-4 anemia. (p=0.021).
  
  
  CONCLUSIONS
  Certain SNPs of KDR may affect treatment outcome and toxicity in patients treated with sunitinib.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Korea. hoy.lim@samsung.com.
authors.forename: Chi Hoon
authors.initials: CH
authors.lastname: Maeng
authors.forename: Jun Ho
authors.initials: JH
authors.lastname: Yi
authors.forename: Jeeyun
authors.initials: J
authors.lastname: Lee
authors.forename: Jung Yong
authors.initials: JY
authors.lastname: Hong
authors.forename: Moon Ki
authors.initials: MK
authors.lastname: Choi
authors.forename: Hyun Ae
authors.initials: HA
authors.lastname: Jung
authors.forename: Joon Oh
authors.initials: JO
authors.lastname: Park
authors.forename: Se Hoon
authors.initials: SH
authors.lastname: Park
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Park
authors.forename: Won Ki
authors.initials: WK
authors.lastname: Kang
authors.forename: Ho Yeong
authors.initials: HY
authors.lastname: Lim
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D056726:Genetic Association Studies; D006720:Homozygote; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D000077210:Sunitinib; D017211:Treatment Failure; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; D000077210:Sunitinib
keywords: Single nucleotide polymorphism; VEGF; VEGFR; biliary tract cancer; gastric cancer; sunitinib