Exercise to Reduce Chemotherapy-Induced Peripheral Neuropathy: A Pilot RCT

Abstract

Oxaliplatin-induced peripheral neuropathy (OIPN) occurs in 85-95% of patients receiving FOLFOX or FOLFIRINOX, oxaliplatin-based chemotherapy for invasive gastrointestinal (GI) cancers. Persistent OIPN can impair long-term quality of life (QOL). No OIPN cures are known. Aerobic physical activity (PA) may reduce OIPN by enhancing circulation and re-distributing neurotoxic oxaliplatin away from vulnerable neurons. However, no trials have evaluated solely aerobic exercise for OIPN. This dissertation reports the results of a 1) literature review on exercise for chemotherapy-induced peripheral neuropathy, and 2) pilot randomized controlled trial (RCT) of brisk walking for OIPN in FOLFOX/FOLFIRINOX-receiving GI cancer survivors. The “MI-Walk Intervention”—an eight-week motivational enhancement therapy (MET)- home-based aerobic walking intervention—was tested in this study. The RCT aims were to explore the 1) effect of the MI-Walk Intervention on eight-week OIPN severity and QOL compared to PA education alone, and 2) intervention feasibility among patients receiving FOLFOX/FOLFIRINOX. The primary hypothesis was that the intervention participants would report less severe OIPN and higher QOL at eight weeks than participants who received PA education alone. Recruitment of 60 GI cancer patients from two cancer clinics occurred at the second FOLFOX/FOLFIRINOX visit. All participants received PA education and regular phone assessments of intervention-related adverse events (the control condition). Half (n=30) received the MI-Walk Intervention, which included theory-based motivational supports (e.g., a Fitbit Charge 2, three MET sessions, and goals worksheets). Ongoing peer support was encouraged via peer email, phone, and walking groups. Self-report surveys of OIPN (primary outcome) and QOL were administered pre-and post-intervention. Feasibility, including intervention acceptability survey scores, were also explored. Intergroup differences at eight weeks were explored using multiple imputation for intention-to-treat linear regression analyses. Linear mixed model regression was used to evaluate intergroup differences in PA. Randomization was stratified by clinic and diabetes diagnosis. The enrollment and completion rates were 62% (N = 57) and 87%, respectively. The intervention compared to the control condition had no effect on sensory OIPN (mean difference [MD] = -0.01; p > .99), motor OIPN (MD = 2.39; p = .17) and QOL (MD = -1.43; p > .99). Eight-week sensory (mean = 11.48 ± 0.38) and motor OIPN severities (mean = 7.48 ± 0.36) both increased from baseline (p ≤ .01) but were mild. The intervention group’s Fitbit-measured weekly minutes of aerobic PA increased from baseline to eight weeks (MD = 17.39; p = .03). However, self-reported PA increases over time were slightly higher on average in the control than the intervention group (MD = -24.02; p = .30). Satisfaction with the intervention was high (mean = 4.32 ± 0.9), but overall acceptability scores were low (MD = 47.91 ± 11.45); the Fitbit and MET were rated most helpful in encouraging walking; the email and walking groups were unhelpful. No adverse events were noted. This study failed to detect significant beneficial effects of aerobic walking on OPIN, however small sample size and notable PA increases in the control group suggest that further research is necessary in order to replicate or refute our null findings among GI cancer survivors receiving FOLFOX/FOLFIRINOX. Although OIPN severities increased (indicating aerobic exercise may not completely prevent OIPN), they were mild at eight weeks. Some intervention components were “unhelpful.” Studies are needed to identify the most helpful intervention components to tailor interventions for individuals receiving FOLFOX/FOLFIRINOX.