Can Exercise Ease 'Chemobrain' During Chemotherapy?

Simple exercises performed during chemotherapy may significantly reduce treatment-related cognitive impairment, according to findings from a phase 3 randomized controlled trial.

Among patients with cancer receiving 2-week cycles of chemotherapy, a structured and individualized exercise “prescription” combining walking and resistance band training significantly reduced cognitive impairment and mental fatigue compared with usual care.

The results are “practice-changing,” colead author Karen Mustian, PhD, MPH, with the Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York, told Medscape Medical News. “Cancer care providers should consider incorporating structured, home-based exercise programs, such as walking and resistance band exercises, into routine chemotherapy care.”

The findings, published online in the Journal of the National Comprehensive Cancer Network (NCCN), reinforce recommendations by the NCCN that survivors with cancer-related cognitive dysfunction engage in routine physical activity.

“Many patients who need chemotherapy worry that they’ll experience ‘chemo brain,’” Lindsay L. Peterson, MD, medical oncologist at Washington University School of Medicine in St. Louis, who was not involved in this research, added in a statement.

This study offers “encouraging news” — exercise may be something patients can do to reduce their risk for cognitive impairment during chemotherapy, Peterson said.

Less Brain Fog, Mental Fatigue

Up to three-fourth of patients experience cancer-related cognitive impairment during treatment, which often occurs alongside mental fatigue. Research assessing the effects of exercise on cancer-related cognitive impairment during treatment is limited. To investigate, Mustian and colleagues enrolled 687 chemotherapy-naive adults with various cancers as well as Karnofsky performance status scores of at least 70 and no physical limitations, who were scheduled to start chemotherapy with cycles of 2, 3, or 4 weeks. Participants were randomly assigned to either the Exercise for Cancer Patients (EXCAP) intervention or usual care while undergoing chemotherapy. Developed by Mustian and colleagues, EXCAP is a 6-week, home-based, individually tailored walking and resistance band exercise program, introduced during a single in-person training session and reinforced through follow-up calls.

Before chemotherapy began, participants in both groups averaged roughly 2 miles of walking daily. After 6 weeks, patients in the EXCAP group largely maintained their activity levels, while those receiving usual care reduced their daily steps by about half. The exercise group also added resistance-band training three times per week for about 25 minutes per session, while the usual care group did no resistance exercises.

Cognitive function was measured using the Functional Assessment of Cancer Therapy-Cognitive Function questionnaire, and mental fatigue was assessed using the Multidimensional Fatigue Symptom Inventory. Blood samples were collected to measure key inflammatory markers.

Overall, across the study population, cognitive function declined and mental fatigue worsened during chemotherapy, but outcomes differed by treatment group and chemotherapy schedule.

Patients assigned to EXCAP and receiving chemotherapy on 2-week cycles fared best. More specifically, compared with usual care, EXCAP participants undergoing 2-week chemotherapy cycles reported less overall cognitive impairment (mean difference, 7.0; P = .04) and lower perceived cognitive impairment (mean difference, 4.1; P = .05). The exercisers also received fewer perceived comments from others about cognitive difficulties (mean difference, 0.6; P = .02) and reported less mental fatigue (-1.6; P < .01).

These benefits, however, were not observed in patients receiving 3- and 4-week chemotherapy cycles. In the 3-week cohort, there were no significant differences between groups in cognitive impairment (mean difference, 0.5; P = .85) or mental fatigue (mean difference, -0.2; P = .60).

“This was surprising,” Mustian said. “We really don’t know why the patients receiving chemo every 2 weeks were the ones to benefit the most. We do not have the capacity in our current data to answer that question for sure.”

However, Mustian speculated that it’s possible patients who receive their chemotherapy on differing weekly schedules receive different chemotherapy agents that have different toxicity and adverse-effect profiles.

For instance, chemotherapy among patients on a 2-week cycle may come with less severe acute adverse effects, which in turn may allow patients to remain more active throughout their treatments. On the other hand, chemotherapy among patients on a 3-week cycle may come with more severe acute adverse effects, which prevent them from staying as active.

“Once a person starts to lower their activity levels, it is more difficult to get back to their baseline levels and maintain them, and definitely harder to add anything additional to their activity routines,” Mustian said.

Immune Benefits?

Mustian and her team also assessed ties between exercise, cognitive impairment, and inflammation during chemotherapy. Previous work from the team showed that patients who received the EXCAP intervention exhibited higher immunocompetence.

In the current study, the researchers observed that a “healthy inflammatory response” — reflecting balanced increases in both proinflammatory and anti-inflammatory cytokines — was associated with better cognitive outcomes, suggesting that immune regulation may play a role in chemotherapy-related cognitive symptoms.

While chemotherapy may contribute to cognitive impairment by disrupting the body’s inflammatory and immune responses, “exercise may help keep these body systems working more normally, which could explain why patients who exercised had better thinking and less mental fatigue,” Mustian said.

Role for Exercise Oncology

Mustian suggested that oncologists consider referring patients receiving chemotherapy to exercise oncology specialists who can tailor programs for individual capabilities.

There are now > 2000 exercise oncology programs across the US. “Many of them provide both in-person and remote online opportunities for patients to access highly qualified exercise oncology professionals,” Mustian said.

Taking time to learn about community resources, developing a referral method of referral, or even providing patients with simple handouts on credible exercise programs and NCCN guidelines can help, Mustian added.

Peterson noted that, for many patients, maintaining the ability to think clearly, remember details, and stay mentally engaged during treatment is essential to preserving independence, continuing to work and care for their families, and sustaining overall quality of life.

“Interventions that are accessible and low cost, such as structured physical activity, give us a powerful opportunity not only to support long-term survivorship, but to help patients remain as cognitively sharp and mentally resilient as possible throughout treatment,” Peterson said in a statement.

This study was supported by the National Cancer Institute. Mustian and Peterson reported having no relevant disclosures.

A version of this article first appeared on Medscape.com.