Preventive effect of sensorimotor exercise and resistance training on chemotherapy-induced peripheral neuropathy: a randomised-controlled trial

Jana Müller, Markus Weiler, Andreas Schneeweiss, Georg Martin Haag, Karen Steindorf, Wolfgang Wick, Joachim Wiskemann, Jana Müller, Markus Weiler, Andreas Schneeweiss, Georg Martin Haag, Karen Steindorf, Wolfgang Wick, Joachim Wiskemann

Abstract

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, unpleasant and usually long-lasting side effect of neurotoxic chemotherapeutic agents. This study aimed to investigate the preventive potential of sensorimotor- (SMT) and resistance training (RT) on CIPN.

Methods: Patients (N = 170) were randomised to SMT, RT or usual care (UC). Both exercise groups trained 3×/week for a total of 105 min/week during neurotoxic chemotherapy (mean length: 20 weeks). Before and 3 weeks after neurotoxic chemotherapy, CIPN signs/symptoms were assessed via Total Neuropathy Score (TNSr; primary endpoint) and EORTC QLQ-CIPN15 questionnaire. In addition, balance (centre of pressure), muscle strength (isokinetic), quality of life (QoL, EORTC QLQ-C30) and relative chemotherapy dose intensity (RDI) were investigated. The follow-up period covered 6 months after the end of chemotherapy.

Results: Intention-to-treat analyses (N = 159) revealed no differences regarding CIPN signs/symptoms. Exploratory per-protocol analyses (minimum training attendance rate 67%; N = 89) indicated that subjectively perceived sensory symptoms in the feet increased less during chemotherapy in the adherent exercisers (pooled group: SMT+RT) than in the UC group (-8.3 points (-16.1 to -0.4); P = 0.039, ES = 1.27). Furthermore, adherent exercisers received a higher RDI (96.6 ± 4.8 vs. 92.2 ± 9.4; P = 0.045), showed a better course of muscular strength (+20.8 Nm (11.2-30.4); P < 0.001, ES = 0.57) and QoL (+12.9 points (3.9-21.8); P = 0.005, ES = 0.64). During follow-up, CIPN signs/symptoms persisted in all groups.

Conclusions: This study demonstrates that SMT and/or RT alleviate subjectively perceived sensory CIPN symptoms in the feet and other clinically relevant cancer therapy-related outcomes, if an appropriate training stimulus is achieved.

Clinical trial registration: NCT02871284.

Conflict of interest statement

The authors declare no competing interests.

© 2021. The Author(s).

Figures

Fig. 1. Study design.
Fig. 1. Study design.
CIPN chemotherapy-induced peripheral neuropathy, pre assessment point before neurotoxic chemotherapy, post0 assessment point 3 weeks after neurotoxic chemotherapy, post3 assessment point 3 months after post0, post6 assessment point 6 months after post0, R randomisation.
Fig. 2. CONSORT flow chart.
Fig. 2. CONSORT flow chart.
Pre assessment point before neurotoxic chemotherapy, post0 assessment point 3 weeks after neurotoxic chemotherapy, post3 assessment point three months after post0, post6 assessment point six months after post0.
Fig. 3. Effect sizes for CIPN signs…
Fig. 3. Effect sizes for CIPN signs and symptoms and other symptoms associated with anticancer therapy (pre–post0, PPEX analysis).
CMAP compound muscle action potential of peroneal nerve, NCV nerve conduction velocity, QoL quality of life, SNAP sensory nerve action potential of sural nerve, TNSc Total Neuropathy Score (clinical), TNSm Total Neuropathy Score (modified), TNSr Total Neuropathy Score (reduced).

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