**Background:** Cancer cachexia (CC) affects approximately half of all patients with advanced cancer, rising above 80% in the last weeks of life. It is characterized by anorexia, systemic inflammation, muscle loss, and weight loss, severely impacting quality of life. Evidence supports personalized, multi-targeted, multimodal interventions, but patient compliance is challenging, with dropout rates around 20% in palliative care settings. Exercise may reduce CC effects by modulating muscle metabolism and inflammation, but evidence in advanced disease is limited. Psycho-social interventions addressing eating-related distress and caregiver burden are also needed. This study aimed to evaluate the feasibility of combining a psycho-educational intervention with an exercise program for dyads (patients and caregivers) managed by a specialized palliative care team (SPCT).
**Methods:** This prospective mixed-methods single-arm feasibility trial was conducted between March 2019 and September 2021 at S. Maria Nuova Hospital, Reggio Emilia, Italy. A convenient sample of 30 consecutive cancer patients with cachexia or refractory cachexia (assessed by ESPEN guidelines and MUST) and their caregivers was planned. Inclusion criteria: age >18 years, good Italian language command, written informed consent, histologically confirmed cancer, and identified caregiver. Exclusion criteria: major mental disorder/dementia, severe sensory deficit, diffuse bone metastases at fracture risk. The intervention included: (1) psycho-educational component—3 weekly dyadic meetings led by three trained nurses covering changing eating habits, food management strategies, and re-evaluation of needs, supported by an information booklet; (2) rehabilitative component—3 outpatient physiotherapist sessions plus at least 24 home-based exercise sessions over 8 weeks, including strengthening, stretching, and relaxation exercises tailored to the patient. Feasibility was defined as completion rate ≥50% for both components. Secondary outcomes included patient QoL (FAACT), caregiver burden (Zarit Burden Scale), hand-grip strength, 30-s sit-to-stand test, and qualitative acceptability via semi-structured interviews with dyads and a focus group with healthcare professionals.
**Key Results:** Twenty-four dyads consented to participate (80% of planned target). Seven patients refused due to the demanding schedule; 47 were ineligible (poor prognosis n=30, no caregiver n=9, language n=4, other n=4). Twenty dyads received at least two psycho-educational sessions (feasibility 83.3%, 95% CI 62.6–95.3). Six dyads participated in at least 14 of 27 exercise sessions (feasibility 25.0%, 95% CI 9.8–46.7). Only six dyads (25.0%) showed >50% compliance for both components, so the primary feasibility endpoint was not met. Eighteen patients withdrew: death (n=1), clinical deterioration (n=16), transportation difficulties (n=1). Twelve of 24 patients (50%) died within 3 months of enrollment. Among the six completers, QoL (FAACT) remained stable (T0 mean 15.50 vs T2 mean 15.17), caregiver burden (Zarit) was stable (T0 mean 17.83 vs T2 mean 17.50), hand-grip strength was maintained (T0 21.90 kg vs T3 20.69 kg), and sit-to-stand performance slightly improved (T0 9.17 reps vs T3 9.80 reps). Qualitative analysis from six interviewed dyads and five healthcare professionals (3 nurses, 2 physiotherapists) revealed high acceptability: dyads appreciated the dedicated space to discuss CC, personalized exercise, and the dyadic approach. Healthcare professionals noted challenges including rapid patient deterioration, the need for inter-professional coordination, and the difficulty of working with late-stage patients.
**Clinical Implications:** This pilot study demonstrates that while a bimodal psycho-educational and exercise intervention for cancer cachexia is highly acceptable to patients and caregivers, its feasibility is severely limited by the unpredictable and rapid clinical deterioration typical of advanced cancer. The psycho-educational component was far more feasible (83.3%) than the exercise program (25.0%), likely due to its shorter duration (3 weeks vs 8 weeks). The 50% mortality within 3 months of enrollment indicates that prognostic screening tools (e.g., Palliative Prognostic Index) should be used to better select patients. Future trials should consider shorter intervention periods (maximum 1 month), flexible delivery (including telerehabilitation), and integration of healthcare professionals already embedded in clinical teams rather than research-specific staff. Outcome measures should focus on patient-reported outcomes and quality of life rather than performance-based tests alone. The dyadic approach was valued and should be maintained in future studies.