The influence of exercise on the mediational relationship between chemotherapy-induced sensory neuropathy and cancer-related fatigue: A nationwide phase II RCT in 111 patients receiving chemotherapy.

12151 Background: Cancer-related fatigue (CRF) and chemotherapy-induced sensory neuropathy (e.g., numbness, tingling, and pain) are common, sometimes debilitating toxicities that often co-occur in patients receiving neurotoxic chemotherapy. Both CRF and sensory neuropathy significantly diminish daily function and quality of life. Exercise is recommended for treating CRF and may also alleviate sensory neuropathy. Whether exercise-induced reductions in CRF are mediated by improvements in sensory neuropathy remains unknown. Methods: We conducted a nationwide phase II randomized controlled trial (RCT) through the University of Rochester Cancer Center NCI Community Oncology Research Program (URCC NCORP) Research Base. Patients who received neurotoxic chemotherapy in the past 9 months and developed moderate or severe (rated ≥4 on a 0-10 numerical scale) chemotherapy-induced sensory neuropathy (e.g., numbness, tingling, hot/burning or sharp/shooting pain in the hands and feet) in the past 2 weeks were randomized to virtually delivered Exercise for Cancer Patients (vEXCAP) or usual care (UC). vEXCAP is a 6-week, individually tailored, progressive walking and resistance band exercise intervention delivered virtually. CRF severity and sensory neuropathy were assessed via the Brief Fatigue Inventory severity score and the EORTC QLQ-CIPN20 sensory subscale (0-100 scale), respectively, at pre- and post-intervention. Causal mediation analyses were conducted to determine the extent to which exercise-induced improvements in CRF were mediated by changes in sensory neuropathy at post-intervention. Results: One hundred eleven patients (mean age 59.5 years; 76% female; 84% white; 37% breast cancer; 36% gastrointestinal cancer) were randomized and completed pre- and post-intervention assessments. vEXCAP participants, compared to UC participants, experienced significantly greater reductions in CRF (-0.95±0.33, p = 0.014) and clinically meaningful improvements in sensory neuropathy at post-intervention (-5.38±2.77 [MCID = 4.2], p = 0.055). Causal mediation analyses indicated that reductions in sensory neuropathy significantly mediate exercise-induced improvements in CRF severity (-0.18±0.13, p = 0.056), accounting for 19% (95% CI: 0% - 64%) of the exercise effect on CRF severity at post-intervention. Conclusions: vEXCAP reduces CRF severity and chemotherapy-induced sensory neuropathy among patients receiving neurotoxic chemotherapy. Approximately 19% of the exercise-induced improvements in CRF severity are mediated by reductions in chemotherapy-induced sensory neuropathy. Future Phase III RCTs are needed to confirm these findings and further explore the mediational role of chemotherapy-induced sensory neuropathy on CRF to help optimize the treatment of CRF using exercise. Clinical trial information: NCT04888988 .