CRP levels and higher neutrophils in this group were also negatively correlated with the domain score inhibitor Lapatinib Learning Memory. In the VEGFR TKI patients higher ESR, CRP and LDH levels were associated with higher scores on the BDI II, indicating more depressive symptoms. No correlations were found between the free testosterone or estradiol levels and the results on the neuropsychological tests or the self report questionnaires. In both patient groups, the VEGF levels were not asso ciated with the results on the cognitive domain scores or fatigue. Only in the patient control group higher VEGF levels were associated with less complaints on mood, psychological well being and cognitive failure in daily functioning. We were able to analyze serum cytokine levels in 29 VEGFR TKI patients and 18 patient controls.

In both groups no detectable Inhibitors,Modulators,Libraries levels of IL 5 and IL 6 were found in any of the patients, and IL 2 and TNF levels were only sporadically detected. The IL 8 level was detectable in 80% of the VEGFR TKI group and in 67% of the patient controls and no difference was found in IL 8 levels between the patient groups. We found no correlations between the serum IL 8 level and the scores on the neuropsychological tests or the self report questionnaires. No correlations were found between the duration of treatment with VEGFR TKI and biomarker concentrations or the results of the neuropsychological tests and the self report questionnaires, except for the results on the subdomain Working Memory and the CIS20r.

Discussion This study is the first to examine cognitive functioning and subjective cognitive complaints in cancer patients during treatment with the VEGFR TKI sunitinib or sora fenib. Inhibitors,Modulators,Libraries We found that these patients performed worse on the cognitive domains Learning Memory and Executive Functions compared to healthy controls. Furthermore, a longer duration Inhibitors,Modulators,Libraries of VEGFR TKI treatment was associated with worse functioning on Work ing Memory tasks. Patient controls also Inhibitors,Modulators,Libraries showed impair ments on the neuropsychological tests concerning Learning Memory. However, in contrast with the VEGFR TKI patients, they showed im pairment only on the subdomain Problem Solving but not on Response Generation. Our data suggest that effect sizes of cognitive dysfunction in patients using VEGFR TKI are larger on the domains Memory Learning and Executive Functions, compared to patient controls.

Although we found no significant differences in the results of the neuro psychological tests between the VEGFR TKI patients and the patient controls, possibly due to the smaller group Inhibitors,Modulators,Libraries size of the patient control group. Since both patient groups performed on the domain Attention Concentration the same as the healthy con trols, the observed deficits in kinase inhibitor Sorafenib the other domains are not due to worse attention and concentration.