Timing and specificity of the cognitive changes induced by interleukin-2 and interferon-alpha treatments in cancer patients.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
These findings suggest the existence of early differential neuropsychological changes in patients treated with IL-2 and IFN-alpha.
Capuron
L
L
INSERM U394, Neurobiologie Intégrative, Institut François Magendie, Bordeaux, France. lcapuro@emory.edu
Ravaud
A
A
Dantzer
R
R
D000276:Adjuvants, Immunologic / Q000009:adverse effects*; D000328:Adult; D003072:Cognition Disorders / Q000139:chemically induced* / Q000175:diagnosis; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects*; D016899:Interferon-beta / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000523:psychology*; D009483:Neuropsychological Tests; D012680:Sensitivity and Specificity; D013028:Space Perception / Q000502:physiology; D013997:Time Factors
D000276:Adjuvants, Immunologic; D016898:Interferon-alpha; D016899:Interferon-beta