title: Pilot trial of sunitinib therapy in patients with von Hippel-Lindau disease.
abstract: BACKGROUND
  Von Hippel-Lindau (VHL) disease induces vascular neoplasms in multiple organs. We evaluated the safety and efficacy of sunitinib in VHL patients and examined the expression of candidate receptors in archived tissue.
  
  
  METHODS
  Patients with VHL were given four cycles of 50 mg sunitinib daily for 28 days, followed by 14 days off. Primary end point was toxicity. Modified RECIST were used for efficacy assessment. We evaluated 20 archival renal cell carcinomas (RCCs) and 20 hemangioblastomas (HBs) for biomarker expression levels using laser-scanning cytometry (LSC).
  
  
  RESULTS
  Fifteen patients were treated. Grade 3 toxicity included fatigue in five patients. Dose reductions were needed in 10 patients. Eighteen RCC and 21 HB lesions were evaluable. Six of the RCCs (33%) responded partially, versus none of the HBs (P = 0.014). LSC revealed that mean levels of phosphorylated vascular endothelial growth factor receptor-2 were lower in HB than in RCC endothelium (P = 0.003) and mean phosphorylated fibroblast growth factor receptor substrate-2 (pFRS2) levels were higher in HB (P = 0.003).
  
  
  CONCLUSIONS
  Sunitinib treatment in VHL patients showed acceptable toxicity. Significant response was observed in RCC but not in HB. Greater expression of pFRS2 in HB tissue than in RCC raises the hypothesis that treatment with fibroblast growth factor pathway-blocking agents may benefit patients with HB.
authors: Departments of Genitourinary Medical Oncology. Electronic address: ejonasch@mdanderson.org.
authors: E
authors: E
authors: Jonasch
authors: Neurosurgery.
authors: I E
authors: IE
authors: McCutcheon
authors: Endocrine Neoplasia and Hormonal Disorders.
authors: S G
authors: SG
authors: Waguespack
authors: Biostatistics, The University of Texas M. D. Anderson Cancer Center, Houston.
authors: S
authors: S
authors: Wen
authors: ApoCell, Inc, Houston.
authors: D W
authors: DW
authors: Davis
authors: Departments of Genitourinary Medical Oncology.
authors: L A
authors: LA
authors: Smith
authors: Departments of Genitourinary Medical Oncology.
authors: N M
authors: NM
authors: Tannir
authors: Departments of Ophthalmology.
authors: D S
authors: DS
authors: Gombos
authors: Pathology.
authors: G N
authors: GN
authors: Fuller
authors: Urology, The University of Texas M. D. Anderson Cancer Center, Houston, USA.
authors: S F
authors: SF
authors: Matin
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D018325:Hemangioblastoma / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000000981:diagnostic imaging / Q000188:drug therapy; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy; D010865:Pilot Projects; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use*; D011859:Radiography; D000077210:Sunitinib; D016896:Treatment Outcome; D055815:Young Adult; D006623:von Hippel-Lindau Disease / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib