Phase II study of exercise and low-dose ibuprofen for cancer-related cognitive impairment (CRCI) during chemotherapy

12016 Background: CRCI is a debilitating consequence of cancer and its treatment, including difficulties in attention, memory, and executive function. Though CRCI can develop during the course of chemotherapy, interventions targeting CRCI during chemotherapy have not been investigated. Inflammation contributes to CRCI and thus reducing inflammation may ameliorate CRCI. Using a biobehavioral approach, we investigated 2 promising interventions that reduce inflammation: exercise and low-dose ibuprofen. Methods: This is a Phase II RCT with a 2:2 factorial design. Eligible participants were patients with cancer receiving chemotherapy who self-reported cognitive difficulties. Participants were stratified by disease type (breast cancer; gastrointestinal cancer; other) and were randomized to 1 of 4 groups for 6 weeks: exercise alone (+ placebo), ibuprofen alone, exercise + ibuprofen, or placebo only. The exercise intervention, delivered by an exercise physiologist, was Exercise for Cancer Patients (EXCAP), an individually tailored, home-based prescription of walking and resistance band training. Ibuprofen/placebo was over-encapsulated for blinding; 200mg was taken 2 times per day. Participants completed 7 cognitive assessments probing attention, memory, and executive function including the Trail Making Test (TMT) and self-report (FACT-Cog) at baseline and post-intervention. ANCOVA, controlling for baseline, assessed overall Arm effects at post-intervention. Results: Of the 110 who consented to the study, 86 participants (mean age=54; 88% female; 76% breast cancer, 21% GI; 73% Stage I-III) completed baseline assessments and were randomized to one of four study arms. Ninety percent (78/86) of those completed post-intervention. Average pill compliance across all 4 groups was balanced and averaged 90.8%. Participants in the exercise and exercise + ibuprofen arms increased 2,414 and 1,073 steps respectively compared to those in placebo and ibuprofen arms increased only 464 and 412 steps respectively from pre- to post-intervention. No study-related adverse events occurred. Intent to treat ANCOVA analyses revealed a significant improvement in attention (TMT) in exercise alone compared to placebo (21.57 seconds better; p=0.003), ibuprofen alone compared to placebo (11.27 seconds better; p=0.0475), and trend for exercise + ibuprofen (7.98 seconds better; p=0.122). Those participating in both exercise arms exhibited significant improvements in the FACT-Cog Comments from Others subdomain (p