Pilot trial testing the effects of exercise on chemotherapy-induced peripheral neurotoxicity (CIPN) and the interoceptive brain system.

Autor: Kleckner IR; University of Maryland School of Nursing., Manuweera T; University of Maryland School of Nursing., Lin PJ; University of Rochester Medical Center., Chung KH; Cornell University., Kleckner AS; University of Maryland School of Nursing., Gewandter JS; University of Rochester Medical Center., Culakova E; University of Rochester Medical Center., Tivarus ME; University of Rochester Medical Center., Dunne RF; University of Rochester Medical Center., Loh KP; University of Rochester Medical Center., Mohile NA; University of Rochester Medical Center., Kesler SR; The University of Texas at Austin., Mustian KM; University of Rochester Medical Center.
Jazyk: angličtina
Zdroj: Research square [Res Sq] 2024 Mar 13. Date of Electronic Publication: 2024 Mar 13.
DOI: 10.21203/rs.3.rs-4022351/v1
Abstrakt: Purpose: Chemotherapy-induced peripheral neurotoxicity (CIPN) is a prevalent, dose-limiting, tough-to-treat toxicity involving numbness, tingling, and pain in the extremities with enigmatic pathophysiology. This randomized controlled pilot study explored the feasibility and preliminary efficacy of exercise during chemotherapy on CIPN and the role of the interoceptive brain system, which processes bodily sensations.
Methods: Nineteen patients (65±11 years old, 52% women; cancer type: breast, gastrointestinal, multiple myeloma) starting neurotoxic chemotherapy were randomized to 12 weeks of exercise (home-based, individually tailored, moderate intensity, progressive walking and resistance training) or active control (nutrition education). At pre-, mid-, and post-intervention, we assessed CIPN symptoms (primary clinical outcome: CIPN-20), CIPN signs (tactile sensitivity using monofilaments), and physical function (leg strength). At pre- and post-intervention, we used task-free ("resting") fMRI to assess functional connectivity in the interoceptive brain system, involving the salience and default mode networks.
Results: The study was feasible (74-89% complete data across measures) and acceptable (95% retention). We observed moderate/large beneficial effects of exercise on CIPN symptoms (CIPN-20, 0-100 scale: -7.9±5.7, effect size [ES]=-0.9 at mid-intervention; -4.8±7.3, -ES=0.5 at post-intervention), CIPN signs (ES=-1.0 and -0.1), and physical function (ES=0.4 and 0.3). Patients with worse CIPN after neurotoxic chemotherapy had lower functional connectivity within the default mode network (R 2 =40-60%) and higher functional connectivity within the salience network (R 2 =20-40%). Exercise tended to increase hypoconnectivity and decrease hyperconnectivity seen in CIPN (R 2 = 12%).
Conclusion: Exercise during neurotoxic chemotherapy is feasible and may attenuate CIPN symptoms and signs, perhaps via changes in interoceptive brain circuitry. Future work should test for replication with larger samples. ClinicalTrials.gov identifier NCT03021174.
Competing Interests: Additional Declarations: Competing interest reported. Although we do not believe there are any conflicts of interest, in full disclosure here are the funding sources for this work and any *potential* conflicts of interest: This work was supported by the NCI (UG1CA189961 to KMM and Gary Morrow, R25CA102618 to Gary Morrow, and K07CA221931 to IRK. Resistance bands were generously donated by TheraBand. The authors also acknowledge training that contributed to this manuscript from the TREC Training Workshop (R25CA203650; PI: Melinda Irwin), and support with study logistics and accruals from the Clinical and Translational Science Institute grant support (UL1 TR002001 from the National Institutes of Health [NIH]). This publication was supported by funds from the Maryland Department of Health’s Cigarette Restitution Fund, no. CH-649-CRF (to support AK and IRK). In the last 36 months, JSG received grant funding from the NIH and consulting income from Algo Therapeutix, Eikonizo, and GW Pharma; she also owns vesting shares in Eisana Corp.
Databáze: MEDLINE
Externí odkaz: