Summary: “Chemo brain”—the cognitive fog, memory lapses, and mental fatigue that affect up to 75% of cancer patients—has long lacked a “gold standard” treatment. However, a nationwide Phase 3 clinical trial has found a powerful, low-cost solution: a tailored exercise program called EXCAP.
The study revealed that patients who followed a simple home-based regimen of walking and resistance bands remained mentally sharper and maintained their physical activity levels, while those without a prescription saw their daily movement plummet by 53%.
Key Facts
- The “EXCAP” Prescription: Developed with the American College of Sports Medicine, this program uses progressive aerobic walking and resistance bands tailored to individual abilities.
- Brain Protection: Consistent, mild-to-moderate exercise was shown to reduce cognitive difficulties and improve executive functioning (managing money, medications, and household tasks) during treatment.
- The 53% Drop: Patients without a structured exercise plan reduced their daily walking by half during chemotherapy, whereas those in the exercise group maintained their baseline activity.
- The Two-Week Sweet Spot: Benefits were most pronounced for patients on a two-week chemotherapy schedule, possibly due to lower cumulative toxicity allowing for more consistent activity.
- Anti-Inflammatory Effect: Research confirms that exercise creates a systemic anti-inflammatory environment that supports the immune system during the rigors of cancer treatment.
Source: University of Rochester
Researchers recommended a tailored, scientifically validated exercise program to individuals receiving chemotherapy for cancer, and those who were on a two-week chemotherapy schedule and followed the exercise prescription were able to maintain their walking-step goals, use resistance bands, and stay mentally sharper compared to patients who did not exercise.
Led by Karen Mustian, PhD, MPH, and Po-Ju Lin, PhD, MPH, RD, from the Wilmot Cancer Institute at the University of Rochester, the nationwide study on exercise and cancer is important because:
- Up to 75% of cancer patients report cancer-related cognitive difficulties or “chemo brain.” What is chemo brain? Patients report general brain fog, and trouble managing money, medications, or maintaining a household, for example. Although there is no gold standard treatment for chemo brain, studies have shown that consistent exercise may reduce it and improve executive functioning during and after cancer treatment.
- This study builds on prior research at Wilmot and elsewhere, showing that patients need only undertake mild-to-moderate exercise during cancer treatment to gain benefits. Exercise has an anti-inflammatory effect and promotes a healthy immune system, research confirms.
- In collaboration with American College of Sports Medicine exercise professionals, Mustian developed the exercise prescription (called EXCAP) used in this study. It was designed to provide safe exercise during chemotherapy, and to be practical, low-cost, home-based, and personalized to account for a patient’s physical abilities. It includes progressive aerobic walking and resistance band exercise prescriptions.
The study is featured in the March issue of JNCCN—Journal of the National Comprehensive Cancer Network.
Exercise While on Chemo: How it Helps
“This is a safe and simple exercise prescription that can be an important part of supportive care for anyone going through chemotherapy,” said Mustian, dean’s professor of Surgery, Cancer Control, and associate director of Population Science at Wilmot.
“Cancer care providers should educate their patients about home-based options such as walking and resistance band exercises as part of optimal care, and when needed they should refer patients to exercise oncology specialists can tailor programs to individual capabilities,” she said.
In this phase 3 clinical trial, researchers reported secondary outcomes from an earlier trial that enrolled nearly 700 patients from 20 community oncology clinics across the U.S., who were all receiving chemotherapy for the first time for a variety of cancers.
They were randomized into two groups: standard care without exercise, or the six-week exercise prescription while undergoing chemotherapy. All participants recorded daily steps and exercises.
Prior to receiving chemotherapy, all patients walked an average of 4,000 to 4,500 steps a day. (During chemotherapy, people without a formal exercise prescription typically walk less due to fatigue, weakness, nausea, or other factors, researchers noted.)
In this study, many individuals in the exercise group were able to maintain their usual daily steps while taking chemotherapy, while those who were in the standard-care- without-exercise group reduced their daily steps by 53%.
Patients who exercised while on chemo reported they were also mentally sharper.
Lin believes that having a structured exercise prescription seems to be essential to a good outcome.
“It was striking to find that without a structured exercise prescription, patients receiving chemotherapy reduce their daily walking by half and experience notable increases in problems with thinking, memory, and mental fatigue,” said Lin, a research assistant professor and member of Wilmot’s Cancer Prevention and Control research program.
Why Did Some Patients Benefit More?
The benefits of exercise while on chemo applied mostly to patients who received their treatment every two weeks, as opposed to patients who were getting chemotherapy on three- or four-week cycles.
Scientists are not sure why.
“This needs to be researched further, but speculating, the patients on two-week cycles of chemotherapy may be getting drugs that have different toxicities and less-severe side effects, which may allow them to remain more active,” Mustian said.
“Once a person starts lowering their activity levels, it is more difficult to get back to their baseline activity or maintain it. It may be possible that patients receiving chemotherapy on the three- or four-week cycles were experiencing more toxicity and more side effects.”
Benefits of Exercise
Lin emphasized that regardless of the chemotherapy schedule, “non-pharmacologic” interventions, such as exercise, cognitive training, and mindfulness, are important for managing brain fog because they are safe, easy to use, and can often be delivered at low cost or even at home compared with expensive or clinic-based treatments.
Wilmot offers free evidence-based services for exercise during cancer treatment, nutrition, mindfulness, and massage therapy and a video library for all Wilmot patients through the Pluta Integrative Oncology and Wellness Center in Henrietta.
Additional guidelines for patients interested in exercise during cancer treatment can be found through the National Comprehensive Cancer Network.
The study was carried out through a unique mechanism: The University of Rochester/National Cancer Institute Community Oncology Research Program (NCORP) Research Base, which is a nationwide translational science network to conduct clinical trials.
Key Questions Answered:
A: It’s more than just being tired. Patients describe it as a mental “haze” where they struggle to remember names, lose their train of sight, or find it impossible to manage complex tasks like paying bills or following a recipe. It’s a significant side effect that can derail a patient’s quality of life even when the cancer is being successfully treated.
A: Not at all. The study emphasizes “mild-to-moderate” exercise. The key isn’t intensity; it’s consistency and structure. Even maintaining a baseline of 4,000 steps a day with a few resistance band stretches can be enough to shield the brain from the inflammatory markers that cause cognitive decline.
A: Exercise is a natural anti-inflammatory. Chemotherapy often triggers a massive inflammatory response in the body, which can affect the brain’s “wiring.” By staying active, you are helping your body regulate that inflammation and keeping your immune system robust, which in turn protects your cognitive health.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this exercise and brain cancer research news
Author: Leslie Orr
Source: University of Rochester
Contact: Leslie Orr – University of Rochester
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Effects of Exercise on Cognitive Impairment in Patients Receiving Chemotherapy: A Multicenter Phase III Randomized Controlled Trial” by Karen M. Mustian, Po-Ju Lin, Alisha Chakrabarti, Lindsey J. Mattick, Stephen Samuel, Umang Gada, Brian J. Altman, Paula M. Vertino, Amber S. Kleckner, Ian R. Kleckner, Joseph J. Guido, Chin-Shang Li, Luke J. Peppone, Charles S. Kamen, Kah Poh Loh, Steven R. Rousey, Adedayo A. Onitilo, Marianne Melnik, Supriya G. Mohile, and Michelle C. Janelsins. Journal of the National Comprehensive Cancer Network
DOI:10.6004/jnccn.2025.7118
Abstract
Effects of Exercise on Cognitive Impairment in Patients Receiving Chemotherapy: A Multicenter Phase III Randomized Controlled Trial
Up to 75% of patients report cancer-related cognitive impairment (CRCI) during treatment and up to 10 years posttreatment. CRCI manifests as deficits in attention, verbal memory, executive function, and processing speed.
CRCI frequently co-occurs with mental fatigue. These deficits severely impact treatment adherence, resulting in poor prognosis and increased morbidity and mortality.
Additionally, patients with CRCI and mental fatigue experience considerable difficulty completing activities of daily living (eg, managing medicines and money, driving, shopping, traveling, maintaining the household). Currently, there are no gold-standard treatments for CRCI or mental fatigue.
