Cognitive impairment during chemotherapy is so common that it has its own nickname. “Chemobrain” — a collection of attention problems, verbal memory lapses, and other cognitive deficits — affects roughly three quarters of patients undergoing cancer treatment. For some, the issues persist for years.

Currently, there are no standard treatments for cancer-related cognitive impairment. But two recent clinical trials offer hope that some simple strategies may help.

One, a phase 2 trial published last month in Cancer, involved 86 patients who were undergoing chemotherapy and reporting cognitive difficulties. It found that 6 weeks of structured moderate exercise — daily walking and strength conditioning with resistance bands — improved participants’ performance on some cognitive tests compared to a nonexercising control group. Exercisers also said they were getting fewer “comments from others” about their cognitive acuity. In addition, the trial found benefits, albeit lesser, from low-dose ibuprofen vs placebo.

The findings build upon those from a phase 3 trial published in March in the Journal of the National Comprehensive Cancer Network. Among nearly 700 patients who were beginning chemotherapy, the same 6-week exercise routine lessened the development of treatment-related cognitive symptoms.

The trials are among the first to test interventions for cognitive symptoms while patients are undergoing chemotherapy, rather than after treatment has ended.

Michelle C. Janelsins, PhD, MPH, of the University of Rochester Medicine and Wilmot Cancer Institute in Rochester, New York, worked on both trials and discussed the findings with Medscape Medical News.
The following interview has been edited for length and clarity. 

What was the impetus for these studies?

Cancer-related cognitive impairment is a really important issue for many patients. T hey report problems with memory, problems with processing information, difficulty concentrating, and not being able to handle multitasking to the same degree as before treatment. So we need to develop interventions to help mitigate any cognitive changes that may occur.

Our past research also tells us that we need more trials testing potential interventions during chemotherapy treatment, and specifically ones that include patients who are [already] experiencing cognitive symptoms. Most prior studies have involved patients in the survivorship period — and some of those studies also did not have inclusion criteria for existing cognitive complaints. In [the Cancer] study, we enrolled patients on chemotherapy who were reporting cognitive problems.

Both of these trials looked at structured exercise. Why might exercise be helpful in this setting?

It’s well established that exercise has multiple health benefits for cancer survivors in general. And several studies have shown that the cognitive changes that occur in some patients are associated with increases in inflammation. One of the pathways we think that exercise is eliciting positive effects is through lessening inflammation. But we also know that exercise helps with fatigue and sleep and other things that are often side effects of cancer treatment. So I think it’s a whole-system approach where exercise has multiple health benefits, and acts through several physiologic pathways to help improve cognitive function.

Why did you choose to include ibuprofen in the Cancer study?

In addition to exercise, we also wanted to consider a pharmacologic option because that may be preferred by some patients, or there may be contraindications or limitations to exercise in some cases. So it was really to provide another option, and to test this hypothesis that the interventions might help by alleviating inflammation. Another reason we chose to study ibuprofen is because it’s inexpensive and available over the counter.

The trial assessed the exercise intervention and low-dose ibuprofen — a 200 mg tablet taken twice a day, at least 8 hours apart. We didn’t have any study-related adverse events from either of the interventions. There was good compliance with both, and we saw positive effects with both exercise and low-dose ibuprofen. But the magnitude of effect with exercise was greater. What’s also notable is that the control group showed a worsening in performance on tests that measured attention, but the intervention groups showed a preservation of function, and in some cases, improved function over time.

One group was assigned to exercise and ibuprofen. Is one of your broader aims to figure out whether combination strategies are helpful?

Initially, we were aiming to test whether there was an additive effect from both [exercise and ibuprofen] together. We didn’t really see that. We saw positive effects in some of the outcomes in the combined group but not in an additive way. So what it really tells us is that while both the exercise intervention and low-dose ibuprofen were helpful for cognitive function, in future phase 3 confirmatory studies, we would study them independently.

How can clinicians and patients use this information right now?

I think one of the most important things is that if any patient is experiencing cognitive changes at the beginning of treatment or during treatment, they should bring it up to their medical team and discuss potential interventions that might be appropriate for them. Patients report that these symptoms have a big impact on quality of life. But often, we find that they don’t bring them up.

Now that we have growing evidence of intervention options that can help alleviate some cognitive problems, it’s important for patients to mention any changes they are noticing. We still need phase 3 trials to confirm efficacy, but our data suggests these are two potential options that may be helpful. And with exercise, we always say doing a little is better than doing nothing.

Both trials were funded by the National Cancer Institute. Janelsins had no relevant disclosures.