Timing and Specificity of the Cognitive Changes Induced by Interleukin-2 and Interferon-α Treatments in Cancer Patients

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Abstract
Neuropsychological changes develop in patients treated by cytokine immunotherapy with interleukin-2 (IL-2) and interferon-alpha (IFN-alpha). However, the time course of appearance of these effects remains unclear, and their precise nature is still incompletely characterized. The objective of this study was to assess and characterize the early cognitive changes induced by IL-2 and IFN-alpha in cancer patients at the end of the first week of treatment and to investigate the subsequent evolution of these changes. The study was conducted in 47 cancer patients who received subcutaneous IL-2, administered alone (N = 17) or with IFN-alpha (N = 7), or IFN-alpha alone, administered subcutaneously at low doses (N = 7) or intravenously at high doses (N = 16). An automated battery of neuropsychological tests (Cambridge Neuropsychological Test Automated Battery) was used to measure reaction time, spatial working memory, and planning tasks. Cognitive tests were performed before treatment (day 1) and after 5 days (day 5) and 1 month of treatment. On day 5, patients treated with IL-2 alone had impaired spatial working memory and lower accuracy of planning abilities. In contrast, patients treated with IFN-alpha did not show any impairment in performance accuracy in these tasks but showed longer latencies in the test of reaction time. Most of these early alterations persisted at the end of the first month of treatment without any obvious sign of worsening. These findings suggest the existence of early differential neuropsychological changes in patients treated with IL-2 and IFN-alpha.