IL 6, IL 1 receptor antagonist and tumour necrosis factor alpha levels were related to ratings of fatigue. Only two case reports have been published on neuro behavioral dysfunction during treatment with sunitinib, but these did not include standardized neuropsycho logical definitely assessment tools. The first paper describes three patients with preexisting cerebrovascular Inhibitors,Modulators,Libraries changes who developed severe cognitive and behavioral disorders Inhibitors,Modulators,Libraries during sunitinib treatment, which normalized within one week after discontinuation of sunitinib. The second paper reports two patients who developed severe psy chotic symptoms in the course of sunitinib treatment which also disappeared after cessation of the drug. No studies have been performed Inhibitors,Modulators,Libraries however, examining milder forms of cognitive impairments using validated neuropsychological tests during VEGFR TKI treatment.

This prompted us to examine cognitive functioning and assess subjective cognitive complaints in patients using the VEGFR TKI sunitinib or sorafenib. Since Inhibitors,Modulators,Libraries objective cognitive dysfunction has also been reported in untreated cancer patients, patient controls were included. We conducted a cross sectional study with three study groups, patients with metastatic renal cell cancer or gastrointestinal stromal tumors treated with the VEGFR TKI sunitinib or sorafe nib, patients with mRCC without systemic treatment and healthy controls. Methods Participants and procedure Thirty patients with mRCC or GIST treated with sunitinib or sorafenib for at least 8 weeks, as well as 20 patients with mRCC, not receiving systemic treatment and previously not treated with a VEGFR TKI, were selected to participate in this cross sectional study.

Furthermore, 30 healthy controls were in cluded as reference group from the same socioeconomic background in order to match patients and controls on four important characteristics, which in itself affect cognitive per formance, and cannot be properly Inhibitors,Modulators,Libraries adjusted for statistically. Patients were recruited through their treating specialist, controls were recruited among the acquaintances of the patients and by advertisements in local papers. Eligibility criteria included, age 18 years, Karnofsky Performance Status 70 and fluent in the Dutch language. Par ticipants were excluded if they EtOH had been treated with sys temic chemotherapy or interferon alpha or IL 2 during the last 12 months, had general anesthetics in the last 3 months, were known with brain metastasis, brain in jury, cognitive disorders, or psychiatric or anti epileptic drug use. Age, sex, level of education using a 7 point scoring system and estimated IQ were used for matching purposes. The study was approved by the Medical Review Ethics Committee Region Arnhem Nijmegen and all par ticipants gave written informed consent.