Exercise Linked to Reduction in Chemotherapy-Induced Cognitive Impairment

Karen Michelle Mustian, PhD, MPH

Risk of inflammation and cognitive impairment due to chemotherapy, often called “chemobrain”, may be reduced by maintaining physical activity during treatment, according to a University of Rochester (UR) Medical Center study presented at the 2015 ASCO Annual Meeting.

The randomized, multicenter, phase III study accrued 619 patients with early-stage cancer who were beginning chemotherapy. Eighty-three percent (n = 514) had breast cancer, while 17% (n = 105) had other types of cancer. The mean age was 55 years, and 94% (n = 581) were women. Patients were excluded if they had a diagnosis of leukemia, metastatic disease, or if they were receiving concurrent radiation therapy. Patients had to be sedentary prior to enrollment, which was defined as walking about 4000 steps daily.

Patients were randomized so that half pursued no set exercise regimen during chemotherapy, and the other half were instructed to follow a specific home-based, personalized prescription of aerobic walking and anaerobic resistance band training known as EXCAP (Exercise for Cancer Patients) for 6 weeks. All patients wore a pedometer to track their daily steps.

“Patients were asked to walk on a daily basis and used resistance bands on a daily basis,” said Karen Michelle Mustian, PhD, MPH, lead author on the study and an associate professor in the UR Departments of Surgery and Radiation Oncology, Cancer Control Clinical Research Unit, as well as a Wilmot Cancer Institute researcher. “The regimen is progressively tailored. Based on individual’s baseline exercise level they were asked to increase their steps walked 5% to 20% each week and to progressively increase the intensity in the use of resistance bands.”

Thirty-seven percent of study participants received chemotherapy every 2 weeks (n = 229), 62% received chemotherapy every three weeks (n = 380), and 1% every four weeks (n = 9). Inflammation was assessed at baseline and post intervention using standard serum Luminex assays. Cognitive impairment was evaluated using the FACT-Cognitive Function questionnaire, which identified a total cognitive impairment score, cognitive impairment as perceived by the patient, and cognitive impairment as perceived by others.

The results showed that those in the EXCAP group reported less brain fogginess and memory problems overall, and had lower levels of blood inflammation. They also had improved mobility compared with the non-exercise group.

There was a trend for differences in perceived cognitive ability (P < 0.10) between groups at post-intervention. Follow-up analyses showed exercise participants receiving 2 week cycles of chemotherapy demonstrated less cognitive impairment overall and across all domains (all P < 0.05) except perceived cognitive ability (P < 0.10) than controls at post-intervention. T-tests revealed an exercise-induced anti-inflammatory response with down-regulation of pro-inflammatory cytokines (IFNg, IL-8, IL1b) and up-regulation of anti-inflammatory cytokines (IL-6, IL-10, sTNFra) in exercisers (all P < 0.05). Conversely, t-tests revealed down-regulation of IL-10 and less up-regulation of sTNFra in the control arm (all P < 0.05).

The benefits shown in this study are very promising for early-stage cancer patients undergoing chemotherapy, said Mustian.

“To think that a very simple, low-cost, self-directed exercise prescription can create an anti-inflammatory response similar to a drug and protect against cognitive decline in people with cancer is innovative and very exciting,” she said.

Mustian KM, Janelsins MC, Peppone LJ, et al. EXCAP exercise effects on cognitive impairment and inflammation: a URCC NCORP RCT in 479 cancer patients. J Clin Oncol. 2015;33 (suppl; abstr 9504).