title: Impairment of cognitive functioning during Sunitinib or Sorafenib treatment in cancer patients: a cross sectional study.
abstract: BACKGROUND
  Impairment of cognitive functioning has been reported in several studies in patients treated with chemotherapy. So far, no studies have been published on the effects of the vascular endothelial growth factor receptor (VEGFR) inhibitors on cognitive functioning. We investigated the objective and subjective cognitive function of patients during treatment with VEGFR tyrosine kinase inhibitors (VEGFR TKI).
  
  
  METHODS
  Three groups of participants, matched on age, sex and education, were enrolled; 1. metastatic renal cell cancer (mRCC) or GIST patients treated with sunitinib or sorafenib (VEGFR TKI patients n = 30); 2. patients with mRCC not receiving systemic treatment (patient controls n = 20); 3. healthy controls (n = 30). Sixteen neuropsychological tests examining the main cognitive domains (intelligence, memory, attention and concentration, executive functions and abstract reasoning) were administered by a neuropsychologist. Four questionnaires were used to assess subjective cognitive complaints, mood, fatigue and psychological wellbeing.
  
  
  RESULTS
  No significant differences in mean age, sex distribution, education level or IQ were found between the three groups. Both patient groups performed significantly worse on the cognitive domains Learning & Memory and Executive Functions (Response Generation and Problem Solving) compared to healthy controls. However only the VEGFR TKI patients showed impairments on the Executive subdomain Response Generation. Effect sizes of cognitive dysfunction in patients using VEGFR TKI were larger on the domains Learning & Memory and Executive Functions, compared to patient controls. Both patients groups performed on the domain Attention & Concentration the same as the healthy controls. Longer duration of treatment on VEGFR TKI was associated with a worse score on Working Memory tasks.
  
  
  CONCLUSIONS
  Our data suggest that treatment with VEGFR TKI has a negative impact on cognitive functioning, specifically on Learning & Memory, and Executive Functioning. We propose that patients who are treated with VEGFR TKI are monitored and informed for possible signs or symptoms associated with cognitive impairment.
  
  
  BACKGROUND
  ClinicalTrials.gov Identifier: NCT01246843.
authors.affiliation: Department of Medical Oncology, Radboud University Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands. Sasja.Mulder@radboudumc.nl.
authors.forename: Sasja F
authors.initials: SF
authors.lastname: Mulder
authors.forename: Dirk
authors.initials: D
authors.lastname: Bertens
authors.forename: Ingrid M E
authors.initials: IM
authors.lastname: Desar
authors.forename: Kris C P
authors.initials: KC
authors.lastname: Vissers
authors.forename: Peter F A
authors.initials: PF
authors.lastname: Mulders
authors.forename: Cornelis J A
authors.initials: CJ
authors.lastname: Punt
authors.forename: Dick-Johan
authors.initials: DJ
authors.lastname: van Spronsen
authors.forename: Johan F
authors.initials: JF
authors.lastname: Langenhuijsen
authors.forename: Roy P C
authors.initials: RP
authors.lastname: Kessels
authors.forename: Carla M L
authors.initials: CM
authors.lastname: van Herpen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000503:physiopathology*; D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000139:chemically induced* / Q000175:diagnosis; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects*; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D008568:Memory / Q000187:drug effects; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000503:physiopathology; D009483:Neuropsychological Tests; D009536:Niacinamide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects*; D000077157:Sorafenib; D000077210:Sunitinib
chemical_list: D007211:Indoles; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D009536:Niacinamide; D000077157:Sorafenib; D000077210:Sunitinib