Phase 2 RCT of exercise plus ibuprofen for cancer-related cognitive impairment shows mixed cognitive outcomes.

BACKGROUND: Interventions for cancer-related cognitive impairment are understudied, particularly during therapy. METHODS: Patients with cancer receiving chemotherapy reporting cognitive problems were randomized to one of four study arms for 6 weeks in this phase 2 randomized controlled trial with a 2 × 2 factorial design. Study arms included: Exercise for Cancer Patients©® (EXCAP)-ibuprofen, EXCAP-placebo, ibuprofen only, and placebo only. EXCAP is a home-based, low to moderate-intensity, progressive walking and resistance exercise prescription. Cognitive and biologic assessments were conducted at baseline and post-intervention. RESULTS: Eighty-six participants were randomized (mean age, 53.60; 88.37% female). Between-group analyses showed that participants in the EXCAP-placebo group demonstrated significantly better attention performance on the Trail Making Test compared to the placebo group (-21.57 seconds, p < .001; Cohen's d = -1.31; 95% CI, -2.18 to -0.44; lower times indicate better performance). The ibuprofen only group showed greater improvements than the placebo group (-11.27-second difference, p = 0.05; Cohen's d = -0.73; 95% CI, -1.57 to 0.11). Both EXCAP-ibuprofen and EXCAP-placebo participants exhibited improvements on the FACT-Cog "comments from others" compared to placebo (Cohen's d = 1.00; 95% CI, 0.35 to 1.65 and Cohen's d = 0.65; 95% CI, -0.01 to 1.31). On Rapid Visual Processing mean latency, participants in the EXCAP-placebo group had a significant improvement compared to placebo (Cohen's d = -1.10; 95% CI, -1.97 to -0.23); those receiving ibuprofen had an improvement compared to placebo, which revealed a trend after adjusting for reading score (Cohen's d = -1.04; 95% CI, -2.06 to -0.01). The ibuprofen group performed less well on the Hopkins Verbal Learning Test-Revised delayed compared to those not receiving ibuprofen (Cohen's d = -0.64; 95% CI, -1.21 to -0.07). CONCLUSIONS: Exercise and low-dose ibuprofen improved some domains of cognitive function, although effects were not observed across all measures. Phase 3 trials are needed.