A URCC NCORP Research Base nationwide phase II randomized controlled trial (RCT) investigating the effect of exercise on chemotherapy-induced peripheral neurotoxicity (CIPN).

12014 Background: Over 60% of patients with cancer receiving taxane, platinum, or other neurotoxic agents experience CIPN, which presents as numbness, tingling, and sometimes pain in the hands and feet. CIPN reduces quality of life and can increase mortality by limiting chemotherapy dose. With extremely limited treatments for CIPN, exercise has emerged as one of the most promising yet unproven treatments with no Phase III RCTs to date. Methods: This phase II RCT examines the effect of exercise on CIPN in the University of Rochester Cancer Center (URCC) NCI Community Oncology Research Program (NCORP) Research Base network, recruiting 111 patients across 37 community oncology practices spanning 11 states in the US. Key eligibility include receiving neurotoxic chemotherapy (taxane, platinum, vinca alkaloid, etc.) in the past 9 months and reporting symptoms of CIPN (≥ 4 of 10 at its worst in the past 2 weeks). Participants were randomized 1:1 to 6 weeks of usual care (UC) or virtually delivered Exercise for Cancer Patients (vEXCAP). vEXCAP is a virtually delivered, standardized, individualized, moderate-intensity, home-based, progressive walking and resistance exercise program. We assessed CIPN both pre- and post-intervention using patient-reported CIPN-20 (0-100 scale) and tactile sensitivity in the finger and toe using monofilaments. Each night, participants rated numbness/tingling in the hands/feet on a 0-10 scale. The primary outcome was CIPN-20 total score with CIPN-20 sensory and motor subscales as exploratory. Results: The 111 patients were 59.5 ±10.5 yrs, 76% female, 83% White, 37% breast cancer, 36% gastrointestinal cancer. Exercise yielded statistically and clinically meaningful improvements in CIPN sensory symptoms compared to UC (ΔCIPN-20 = -4.7 [MCID = 4], effect size [ES] = -0.27, p = 0.049). Exercise had a weak effect on CIPN motor symptoms (ΔCIPN-20 = 1.5, ES = 0.08, p = 0.936) and the CIPN-20 total score (ΔCIPN-20 = -1.2, ES = -0.07, p = 0.393). Tactile sensitivity was negatively correlated with CIPN sensory symptoms, as expected (finger: rho = -0.21, p = 0.043, toe: rho = -0.18, p = 0.092). Effects of exercise on tactile sensitivity were beneficial yet small and not statistically significant (ES = 0.04 and 0.07, both p > 0.682). Daily symptom ratings suggest that possible benefits of exercise emerge after 24 days (0.75±0.46 unit reduction, p = 0.104), with clear benefits after 30 days (0.93±0.46 unit reduction, p = 0.045) that grow further through study completion. Conclusions: Six weeks of walking and resistance exercise may reduce CIPN sensory symptoms for patients with CIPN. A future phase III RCT is needed to definitively test for replication and inform clinical practice. Funded by NCI: UG1CA189961, UG1CA189804, UG1CA189822, UG1CA189819, UG1CA189830, R21CA256154, and K07CA221931. Clinical trial: NCT04888988. Clinical trial information: NCT04888988 .