Exercise-based interventions for cancer cachexia: A systematic review of randomised and non-randomised controlled trials.

Objective: Cachexia is a multifactorial syndrome characterised by involuntary weight loss and functional limitation. There is a strong theoretical rationale for the use of exercise in the management of cachexia, and evidence of benefit from exercise in general cancer patients. However, clinical studies of exercise interventions in cancer cachexia are limited. We aimed to synthesise current evidence on the delivery, acceptability, safety and outcomes of exercise interventions for adults with cancer cachexia. Methods: We conducted a systematic review. Four databases were searched up to February 2023 for randomised (RCTs) and non-randomised (NRCTs) controlled studies. Eligibility and quality were independently assessed by two authors. Data on intervention components and structure, participant flow and adherence were tabulated. Clinical outcome data on body stature and composition, muscle strength, functional performance, and health-related quality of life were synthesised using effect direction plots. Results: Twelve studies (9 RCTs, 3 NRCTs) involving a total of 898 patients (study range 20-374) as part of a multicomponent approach. Median programme completion was 75% (range 43%-100%) and adherence was generally high. Five adverse events were considered possibly related to an intervention, including muscle or joint pain, breathlessness on exertion. Overall, 12/16 (75%) outcomes demonstrated a positive direction of effect on body stature and composition, 8/10 (80%) on muscle strength, 14/22 (64%) on functional performance, and 3/8 (38%) on health-related quality of life. Multicomponent interventions showed more consistent effects on body stature, and resistance training interventions on muscle strength. Conclusions: Exercise interventions appear to be safe and acceptable to people with cancer cachexia. Positive effects from exercise are more consistently observed for body stature or composition and muscle strength outcomes, than in functional capacity and health-related quality of life. The synergistic effects of exercise with other cachexia interventions, including drugs, should be examined in future robust studies.