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

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.PHDNursingUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/155080/1/gracekan_1.pd

Proactive Rehabilitation for Chemotherapy-Induced Peripheral Neuropathy

Objective: To review assessment and management approaches for chemotherapy-induced peripheral neuropathy-related physical function deficits.Data sources: Peer-reviewed articles from PubMed, Ovid MEDLINE, CINAHL PsycINFO, SPORTDiscus, Scopus, and key studies\u27 reference lists.Conclusion: Brief clinical tests (eg, gait, Timed Up and Go) can screen for neuropathy-related physical function deficits. Exercise and physical therapy may be promising treatments, but the efficacy and optimal dose of such treatments for chemotherapy-induced peripheral neuropathy are unclear.Implications for nursing practice: Screening and assessment of neuropathy-associated physical function deficits should occur throughout neurotoxic chemotherapy treatment. If such deficits are identified, referral for rehabilitation (ie, physical or occupational therapy) and/or exercise interventions is warranted

Assessment of Pediatric Chemotherapy-Induced Peripheral Neuropathy Using a New Patient-Reported Outcome Measure: The P-CIN

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is commonly experienced by children receiving neurotoxic chemotherapy. No validated pediatric CIPN patient-reported outcome (PRO) measures exist. Purpose: To test sensitivity, internal consistency reliability, content and convergent validity, and feasibility of the Pediatric Chemotherapy-Induced Neuropathy (P-CIN), an electronic PRO measure for assessing CIPN in children who received neurotoxic chemotherapy. Method: Five experts evaluated content validity of the 14-item P-CIN. Children 5 to 17 years old with CIPN (N = 79) completed the P-CIN via tablet computer; a subset (n = 26) also underwent neurological examinations using the Pediatric-Modified Total Neuropathy Score. Following preliminary analyses, one item was deleted and three others modified. The revised P-CIN was retested with patients (n = 6) who also completed the Bruininks-Oseretsky Test of Motor Proficiency motor function assessment. Means, item response ranges, standard deviations, content validity indexes, Cronbach\u27s alphas, and correlation coefficients were calculated. Results: Mean participant age was 11.25 (SD = 4.0) years. Most had acute leukemia (62.5%) and received vincristine (98.7%). Content validity index coefficients ranged from .80 to 1.0 (p = .05). For 9 of 14 items, responses ranged from 0 to 4 or 5; response ranges for toe numbness, pick up a coin, and three of four pain items were 0 to 3. After deleting one item, Cronbach\u27s alpha coefficient was .83. P-CIN scores were strongly associated with Pediatric-Modified Total Neuropathy Score (r = .52, p \u3c .01) and Bruininks-Oseretsky Test of Motor Proficiency (r = -.83, p = .04) scores. Sixty-eight percent of children 6 to 17 years old completed P-CIN independently. Discussion: Preliminary evidence suggests that the 13-item P-CIN is internally consistent, is valid, and can be completed independently by children ≥ 6 years. However, we recommend additional testing

Optimal outcome measures for assessing exercise and rehabilitation approaches in chemotherapy-induced peripheral-neurotoxicity: Systematic review and consensus expert opinion

Introduction: Chemotherapy-induced peripheral neurotoxicity (CIPN) remains a significant toxicity in cancer survivors without preventative strategies or rehabilitation. Exercise and physical activity-based interventions have demonstrated promise in reducing existing CIPN symptoms and potentially preventing toxicity, however there is a significant gap in evidence due to the lack of quality clinical trials and appropriate outcome measures. Areas covered: The authors systematically reviewed outcome measures in CIPN exercise and physical rehabilitation studies with expert panel consensus via the Peripheral Nerve Society Toxic Neuropathy Consortium to provide recommendations for future trials. Across 26 studies, 75 outcome measures were identified and grouped into 16 domains within three core areas - measures of manifestations of CIPN (e.g. symptoms/signs), measures of the impact of CIPN and other outcome measures. Expert opinion: This article provides a conceptual framework for CIPN outcome measures and highlights the need for definition of a core outcome measures set. The authors provide recommendations for CIPN exercise and physical rehabilitation trial design and outcome measure selection. The development of a core outcome measure set will be critical in the search for neuroprotective and treatment approaches to support cancer survivors and to address the significant gap in the identification of effective rehabilitation and treatment options for CIPN