April 27, 2026
5 min read
Key takeaways:
- An exercise intervention improved cognitive function among people undergoing chemotherapy.
- Low-dose ibuprofen may help but the benefits were less consistent, highlighting a need for more research.
Exercise and low-dose ibuprofen may help improve some aspects of cognitive function for people with cancer undergoing chemotherapy, according to results of a randomized phase 2 trial.
The benefits with ibuprofen appeared less robust and consistent than those observed with exercise, underscoring the need for additional research to better understand its effects.
“There 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 — specifically low-dose ibuprofen — as another possible intervention to alleviate cognitive changes,” Michelle C. Janelsins, PhD, MPH, Joan and Gary Morrow Endowed Distinguished Professor of Supportive Care in Cancer at University of Rochester and Wilmot Cancer Institute, told Healio. “It is very exciting to see potential with both behavioral and pharmacologic interventions.”
Interventions needed
As many as 80% of people who undergo chemotherapy experience cancer-related cognitive impairment, according to study background.
The condition — likely due to elevated proinflammatory cytokine levels caused by cancer or its treatments — typically is characterized by mild to moderate problems with memory, concentration, information processing and multitasking.
“Regardless of whether the cognitive changes are subtle or more significant, they can have a big impact on a person’s quality of life, as well as their ability to perform at their job or maintain their home,” Janelsins said. “In 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.”
The researchers hypothesized that the combined use of exercise and ibuprofen — which reduce inflammation via different pathways — could have synergistic benefits.
Most prior research evaluating potential interventions for cancer-related cognitive impairment have been conducted during the survivorship phase.
Janelsins and colleagues enrolled 86 individuals (mean age, 53.6 years; 88.3% women; 91.8% white) receiving curative-intent treatment.
All were undergoing chemotherapy — with at least two treatments completed and two more planned during the study period — and had already reported cognitive difficulties, rating them on a scale of 3 or higher on a 10-point scale.
A majority had breast cancer (75.5%) or gastrointestinal cancer (20.9%).
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).
They conducted biologic and cognitive assessments — measuring memory, attention and executive function — at baseline and after the 6-week intervention period.
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.
Those assigned to EXCAP had a statistically significant increase in number of daily steps from baseline (change, 1,652; P < .001), whereas those assigned to ibuprofen or placebo without exercise did not.
“Most of the people in the study were either sedentary or had low levels of activity,” Janelsins said. “Our 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 — even if only a little bit each week — is much better than nothing.”
Larger benefits with exercise
Researchers used the Trail Making Test, on which a lower time indicates superior performance, to assess attention performance.
Individuals assigned EXCAP plus placebo exhibited significantly improved attention performance than those who received placebo only (–21.57 seconds; P < .001; Cohen’s d = –1.31; 95% CI, –2.18 to –0.44). Individuals assigned ibuprofen alone also showed greater improvement on this measure than participants assigned placebo only (–11.27 seconds; P = .05; Cohen’s d = –0.73; 95% CI, –1.57 to 0.11).
Trail Marking Test performance declined significantly over time among those assigned placebo, a finding that researchers say underscores the need for interventions.
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’s cognitive difficulties.
Results showed greater improvement among those assigned EXCAP plus ibuprofen (Cohen’s d = 1; 95% CI, 0.35-1.65) and EXCAP plus placebo (Cohen’s d = 0.65; 95% CI, –0.01 to 1.31) than those assigned placebo only.
Assessment of rapid visual processing latency — the time necessary for a person’s brain to detect and process visual information — revealed better outcomes among those assigned EXCAP plus placebo (Cohen’s d = –1.1; 95% CI, –1.97 to –0.23) and those assigned ibuprofen only (Cohen’s d = –1.04; 95% CI, –2.06 to –0.01) than those who received placebo only.
Individuals who received ibuprofen exhibited less improvement in short-term verbal memory — as assessed by the Hopkins Verbal Learning Test-Revised — than participants who did not receive ibuprofen (Cohen’s d = –0.64; 95% CI, –1.21 to –0.07), an outcome that researchers acknowledged warrants additional study.
“Overall, while we saw benefits of both exercise and ibuprofen on cognitive outcomes, we did see larger beneficial effects with exercise,” Janelsins said. “Any 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.”
More research needed
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 — including the high rate of white participants and the fact that three-quarters of those enrolled had breast cancer — may limit generalizability of the findings.
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.
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.
“Importantly, we did not see any study-related adverse events with ibuprofen in our study,” Janelsins said. “Because 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.”
For more information:
Michelle C. Janelsins, PhD, MPH, can be reached at michelle_janelsins@urmc.rochester.edu.
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