\u201cThere are already published guidelines that recommend exercise for people undergoing cancer treatment, as well as for survivors, but this is one of the first trials I am aware of to look at an anti-inflammatory medication \u2014 specifically low-dose ibuprofen \u2014 as another possible intervention to alleviate cognitive changes,\u201d Michelle C. Janelsins, PhD, MPH,<\/b> Joan and Gary Morrow Endowed Distinguished Professor of Supportive Care in Cancer at University of Rochester and Wilmot Cancer Institute, told Healio. \u201cIt is very exciting to see potential with both behavioral and pharmacologic interventions.\u201d<\/p>\nInterventions needed<\/h2>\n
As many as 80% of people who undergo chemotherapy experience cancer-related cognitive impairment, according to study background.<\/p>\n
The condition \u2014 likely due to elevated proinflammatory cytokine levels caused by cancer or its treatments \u2014 typically is characterized by mild to moderate problems with memory, concentration, information processing and multitasking.<\/p>\n
\u201cRegardless of whether the cognitive changes are subtle or more significant, they can have a big impact on a person\u2019s quality of life, as well as their ability to perform at their job or maintain their home,\u201d Janelsins said. \u201cIn recent years, the focus of our group and others has really been on conducting longitudinal prospective studies to characterize the problem. We used objective performance-based cognitive and neuropsychological measures to define the magnitude of cognitive changes so, now, identifying appropriate interventions is of utmost importance to our team.\u201d<\/p>\n
The researchers hypothesized that the combined use of exercise and ibuprofen \u2014 which reduce inflammation via different pathways \u2014 could have synergistic benefits.<\/p>\n
Most prior research evaluating potential interventions for cancer-related cognitive impairment have been conducted during the survivorship phase.<\/p>\n
Janelsins and colleagues enrolled 86 individuals (mean age, 53.6 years; 88.3% women; 91.8% white) receiving curative-intent treatment.<\/p>\n
All were undergoing chemotherapy \u2014 with at least two treatments completed and two more planned during the study period \u2014 and had already reported cognitive difficulties, rating them on a scale of 3 or higher on a 10-point scale.<\/p>\n
A majority had breast cancer (75.5%) or gastrointestinal cancer (20.9%).<\/p>\n
Investigators randomly assigned study participants to one of four interventions: placebo (n = 21); low-dose ibuprofen, defined as 200 mg twice daily (n = 22); placebo plus Exercise for Cancer Patients [EXCAP], a validated home-based regimen of low- to moderate-intensity aerobic walking and resistance band exercises (n = 22); or low-dose ibuprofen plus EXCAP (n = 21).<\/p>\n
They conducted biologic and cognitive assessments \u2014 measuring memory, attention and executive function \u2014 at baseline and after the 6-week intervention period.<\/p>\n
Researchers reported high adherence to the pharmacologic interventions, with 89.7% of those assigned ibuprofen or placebo reaching at least 75% pill compliance based on confirmed number of pills remaining at the end of the study period.<\/p>\n
Those assigned to EXCAP had a statistically significant increase in number of daily steps from baseline (change, 1,652; P<\/i> < .001), whereas those assigned to ibuprofen or placebo without exercise did not.<\/p>\n
\u201cMost of the people in the study were either sedentary or had low levels of activity,\u201d Janelsins said. \u201cOur results showed they were able to exercise more, which really drives home the point that having patients do the best they can and try to increase their physical activity \u2014 even if only a little bit each week \u2014 is much better than nothing.\u201d<\/p>\n
Larger benefits with exercise<\/h2>\n Researchers used the Trail Making Test, on which a lower time indicates superior performance, to assess attention performance.<\/p>\n
Individuals assigned EXCAP plus placebo exhibited significantly improved attention performance than those who received placebo only (\u201321.57 seconds; P<\/i> < .001; Cohen\u2019s d = \u20131.31; 95% CI, \u20132.18 to \u20130.44). Individuals assigned ibuprofen alone also showed greater improvement on this measure than participants assigned placebo only (\u201311.27 seconds; P<\/i> = .05; Cohen\u2019s d = \u20130.73; 95% CI, \u20131.57 to 0.11).<\/p>\n
Trail Marking Test performance declined significantly over time among those assigned placebo, a finding that researchers say underscores the need for interventions.<\/p>\n
Investigators used the Functional Assessment of Cancer Therapy-Cognitive Function questionnaire subscale to measure how frequently family members, friends or coworkers comment on or observed a person\u2019s cognitive difficulties.<\/p>\n
Results showed greater improvement among those assigned EXCAP plus ibuprofen (Cohen\u2019s d = 1; 95% CI, 0.35-1.65) and EXCAP plus placebo (Cohen\u2019s d = 0.65; 95% CI, \u20130.01 to 1.31) than those assigned placebo only.<\/p>\n
Assessment of rapid visual processing latency \u2014 the time necessary for a person\u2019s brain to detect and process visual information \u2014 revealed better outcomes among those assigned EXCAP plus placebo (Cohen\u2019s d = \u20131.1; 95% CI, \u20131.97 to \u20130.23) and those assigned ibuprofen only (Cohen\u2019s d = \u20131.04; 95% CI, \u20132.06 to \u20130.01) than those who received placebo only.<\/p>\n
Individuals who received ibuprofen exhibited less improvement in short-term verbal memory \u2014 as assessed by the Hopkins Verbal Learning Test-Revised \u2014 than participants who did not receive ibuprofen (Cohen\u2019s d = \u20130.64; 95% CI, \u20131.21 to \u20130.07), an outcome that researchers acknowledged warrants additional study.<\/p>\n
\u201cOverall, while we saw benefits of both exercise and ibuprofen on cognitive outcomes, we did see larger beneficial effects with exercise,\u201d Janelsins said. \u201cAny intervention must be discussed with a health care professional but, because some individuals may have a contraindication to exercise, this provides another potential alternative to those patients.\u201d<\/p>\n
More research needed<\/h2>\n The researchers acknowledged study limitations, including its small sample size, a lack of significant interaction effects and their inability to assess durability of outcome improvements after treatment cessation. Also, the lack of diversity in the cohort \u2014 including the high rate of white participants and the fact that three-quarters of those enrolled had breast cancer \u2014 may limit generalizability of the findings.<\/p>\n
Overall, though, the findings provide additional evidence to support the potential of exercise and low-dose ibuprofen to improve cancer-related cognitive impairment, researchers concluded. Additional research is needed on biomarker assessments, which could provide important insights into mechanisms, they added.<\/p>\n
Janelsins and colleagues expect to report results soon from a separate larger phase 2 trial that focused specifically on the effects of low-dose ibuprofen on objective and patient-reported outcomes. Those results could help inform a phase 3 trial.<\/p>\n
\u201cImportantly, we did not see any study-related adverse events with ibuprofen in our study,\u201d Janelsins said. \u201cBecause it was safe, one question is whether we could consider a slightly higher dose in a phase 3 trial. If so, might that provide additional benefit? Future larger studies with both exercise and low-dose ibuprofen are planned.\u201d<\/p>\n
For more information:<\/h2>\n Michelle C. Janelsins, PhD, MPH,\u00a0<\/strong>can be reached at michelle_janelsins@urmc.rochester.edu.<\/p>\n\n
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