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Impairment of cognitive functioning during Sunitinib or Sorafenib treatment in cancer patients: a cross sectional study

Sasja F Mulder1*, Dirk Bertens23, Ingrid ME Desar1, Kris CP Vissers4, Peter FA Mulders5, Cornelis JA Punt6, Dick-Johan van Spronsen7, Johan F Langenhuijsen5, Roy PC Kessels23 and Carla ML van Herpen1

Author Affiliations

1 Department of Medical Oncology, Radboud University Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands

2 Department of Medical Psychology, Radboud University Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands

3 Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, PO Box 9104, 6500 HE Nijmegen, The Netherlands

4 Department of Anesthesiology, Pain and Palliative Medicine, Radboud University Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands

5 Department of Urology, Radboud University Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands

6 Department of Medical Oncology, Academic Medical Centre, University of Amsterdam, PO Box 22660, 1100 DD Amsterdam, The Netherlands

7 Department of Internal Medicine, Canisius Wilhelmina Hospital, PO Box 9015, 6500 Nijmegen, The Netherlands

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BMC Cancer 2014, 14:219  doi:10.1186/1471-2407-14-219

Published: 24 March 2014



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).


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.


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.


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.

Trial registration Identifier: NCT01246843.

Cognitive function; Sunitinib; Sorafenib; VEGFR TKI; Memory and Learning; Executive functioning