title: Intrinsic resistance to sunitinib in patients with metastatic renal cell carcinoma.
abstract: OBJECTIVE
  Although targeting angiogenesis with vascular endothelial growth factor receptor (VEGFR) inhibitors has demonstrated efficacy in the treatment of renal cell carcinoma, primary, intrinsic resistance to the VEGFR inhibitor sunitinib is not fully understood in a subset of metastatic RCC (mRCC) patients.
  
  
  METHODS
  Between 2008 and 2012, a total of 134 patients with mRCC were treated with first-line sunitinib at one of six tertiary centers. Patients in whom progressive disease was the best response were classified as the intrinsic resistance group. Univariate and multivariate analyses were performed on the recognized baseline parameters.
  
  
  RESULTS
  Among 134 patients, 33 (25%) intrinsically resistant to sunitinib were identified. Multivariate logistic regression analyses revealed that the number of metastatic sites (OR = 3.6) and neutrophilia (OR = 7.4) were independently associated with development of intrinsic resistance. There were significant differences with regard to overall survival (P = 0.001) and progression-free survival (P < 0.0001) between the patients with and without intrinsic resistance.
  
  
  CONCLUSIONS
  Intrinsic resistance to first-line sunitinib treatment is associated with a dismal prognosis in mRCC patients. Patients with known high-risk factors (poor performance, neutrophilia, elevated lactate dehydrogenase) and multiple metastatic sites including the liver may experience a limited benefit from sunitinib. Greater understanding of the underlying mechanism and molecular biomarkers for detecting intrinsically resistant disease is needed.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Lim
authors.affiliation: Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea.
authors.forename: In Gyu
authors.initials: IG
authors.lastname: Hwang
authors.affiliation: Department of Hematology-Oncology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea.
authors.forename: Jun Ho
authors.initials: JH
authors.lastname: Ji
authors.affiliation: Division of Hematology-Oncology, Dong-A University, College of Medicine, Seoul, Korea.
authors.forename: Sung Yong
authors.initials: SY
authors.lastname: Oh
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Hanyang University Hospital, Seoul, Korea.
authors.forename: Jun Ho
authors.initials: JH
authors.lastname: Yi
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Dankook University Hospital, Cheonan, Korea.
authors.forename: Do Hyoung
authors.initials: DH
authors.lastname: Lim
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Ho Yeong
authors.initials: HY
authors.lastname: Lim
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Se Hoon
authors.initials: SH
authors.lastname: Park
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D011379:Prognosis; D011758:Pyrroles / Q000627:therapeutic use*; D000077210:Sunitinib; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D042461:Vascular Endothelial Growth Factor A; D000077210:Sunitinib
keywords: intrinsic resistance; prognosis; renal cell carcinoma; sunitinib