A clinical trial suggests that exercise, and possibly low-dose ibuprofen, may help counter cognitive decline during chemotherapy.
Cognitive changes are a surprisingly common side effect of chemotherapy, affecting up to 80% of patients. Often described as “brain fog,” these symptoms can include trouble concentrating, memory slips, and difficulty juggling everyday tasks. While usually mild, they can still interfere with work, relationships, and overall quality of life.
A Phase II clinical trial now suggests that both exercise and low-dose ibuprofen may help reduce these symptoms and support cognitive function. The results were published online in CANCER, a peer-reviewed journal of the American Cancer Society.
Exercise and anti-inflammatory drugs have been linked to cognitive benefits in other conditions, but their role during cancer treatment is not well understood. Since both approaches reduce inflammation through different biological pathways, combining them could potentially enhance their effects on cognitive health.
Study Design and Methods
Researchers enrolled 86 chemotherapy patients who reported cognitive issues and randomly assigned them to one of four groups for six weeks: Exercise for Cancer Patients (EXCAP) plus low-dose ibuprofen, EXCAP plus placebo, low-dose ibuprofen alone, or placebo alone. (EXCAP is a home-based program that includes low-to-moderate intensity walking and resistance exercises that gradually increase over time.)
After six weeks, participants in the EXCAP plus placebo group showed significantly better attention compared with those in the placebo group.
Patients who took only ibuprofen also improved more than those receiving a placebo. In addition, participants in both the EXCAP plus ibuprofen and EXCAP plus placebo groups reported fewer noticeable cognitive issues, based on feedback from others such as family members, friends, or coworkers. However, the ibuprofen-only group showed less improvement in short-term verbal memory than those not taking ibuprofen, a result that requires further study.
Interpretation and Implications
The findings indicate that exercise may play a meaningful role in maintaining cognitive function during chemotherapy. Ibuprofen may also provide some benefit, although its effects appear less consistent and may vary depending on the type of cognitive function being measured. Larger Phase III trials will be needed to confirm these results.
“We are encouraged by the findings of this trial that suggest possible benefits of both interventions for some cognitive domains. Clearly, we saw a more pronounced effect with exercise, which is notable considering the multiple health benefits of exercise for cancer survivors,” said lead author Michelle C. Janelsins, PhD, MPH, of the University of Rochester and the Wilmot Cancer Institute. “This is one of the first studies specifically designed to assess these interventions for cancer-related cognitive impairment during chemotherapy in patients with multiple diseases using both performance-based cognitive assessments and patient-reported outcomes.”
Dr. Janelsins added that future research should explore adjusting both the length and dosage of exercise and ibuprofen interventions. She also emphasized that patients should consult a health care provider before trying any approach to manage cognitive symptoms to ensure it is safe and appropriate.
Reference: “Phase 2 trial of exercise and low-dose ibuprofen for cancer-related cognitive impairment in patients receiving chemotherapy” by Michelle C. Janelsins, Riham A. Alieldin, Tyler Holler, Hongying Sun, Po-Ju Lin, Michelle Shayne, Alissa Huston, Kassandra Doyle, Michelle Porto, Mohamedtaki Tejani, Bryan Thompson, Allison Magnuson, Marcia Krebs, Richard F. Dunne, Supriya G. Mohile, Chin-Shang Li, Umang Gada, Ajay Dhakal, Aram F. Hezel, Marcus S. Noel, Alok A. Khorana, Brian D. Yirinec, Nayana Kamath, David W. Dougherty, Tim A. Ahles, Gary R. Morrow and Karen M. Mustian, 20 April 2026, Cancer.
DOI: 10.1002/cncr.70323
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