Feasibility and Effect of Resistance Training and Protein Supplementation in Patients With Advanced Gastroesophageal Cancer

Feasibility and Effect of Resistance Training and Protein Supplementation in Patients With Advanced Gastroesophageal Cancer

Feasibility and Effect of Resistance Training and Protein Supplementation in Patients With Advanced Gastroesophageal Cancer

Patients with advanced gastroesophageal cancer are in great risk of losing skeletal muscle mass and developing cancer cachexia. Low skeletal muscle mass has a negative impact on quality of life, impairs physical function, increases toxicity from anti-neoplastic treatment, as well as increases risk of death. Resistance training and protein supplements have the potential to stimulate muscle anabolism and counteract loss of skeletal muscle mass. Therefore, the investigators have designed a randomized controlled feasibility trial to evaluate the feasibility, safety and the therapeutic effect of resistance training and protein supplements in patients with advanced gastroesophageal cancer undergoing first line chemotherapy. A total of 54 patients with advanced gastroesophageal cancer will be recruited from the Department of Oncology, Copenhagen University Hospital, Rigshospitalet and randomly allocated 2:1 to standard care plus resistance training 3 times pr. week and a daily supplement of protein or to standard care alone.

Exercise oncology, Resistance exercise, Cancer, Cancer cachexia, Protein supplements, Sarcopenia, Palliative chemotherapy

Participants allocated to control receive first line chemotherapy the standard patient care program, as provided by Rigshospitalet, Copenhagen, Denmark. Participants allocated to control are allowed to exercise on their own initiative or participate in any standard care hospital- or municipality-based exercise training program. There will be no diet restrictions.

Participants allocated to intervention receive first line chemotherapy and the standard patient care program, as provided by Rigshospitalet, Copenhagen, Denmark. The intervention consists of resistance training and a daily protein supplement.

SAE will be recorded during trial assessment visits and through medical records. This procedure will concern any SAE during the trial period. For each trial visit we will collect patients' self-report of SAEs, which may have occurred during the period since the last trial visit.

Incidence of exercise intervention disruptions, defined as a period of ≥ 7 days without an attended exercise session

Proportion of patients who have not died from gastroesophageal cancer 1 and 2 years after randomization

Treatment tolerance assessed by the delivery of chemotherapy (permanent discontinuation of the treatment)

Response to chemotherapy assessed by Response Evaluation Criteria in Solid Tumors 1.1 (complete response, partiel response, stable disease, progressive disease)

Changes in patient-reported physical well-being assessed using the Functional Assessment of Cancer Therapy - Esophagus (FACT-E) (scale-scoring 0-28, the higher the score the better quality of life)

Changes in patient-reported social well-being assessed using FACT-E (scale-scoring 0-28, the higher the score the better quality of life)

Changes in patient-reported social well-being assessed using FACT-E (scale-scoring 0-24, the higher the score the better quality of life)

Changes in patient-reported functional well-being assessed using FACT-E (scale-scoring 0-28, the higher the score the better quality of life)

Changes in patient-reported gastroesophageal cancer specific well-being assessed using FACT-E (scale-scoring 0-68, the higher the score the better quality of life)

Changes in patient-reported cancer cachexia specific well-being assessed using Functional Assessment of Cancer Therapy - Cancer Cachexia (scale-scoring 0-48, the higher the score the better quality of life)

Changes in patient-reported depression, assessed using the Hospital Anxiety and Depression Scale (HADS) (scale scoring: 0-21, the higher the score the worse the condition)

Changes in patient-reported anxiety, assessed using the HADS (scale scoring: 0-21, the higher the score the worse the condition)

Changes in patient-reported weekly duration of walking, assessed using the International Physical Activity Questionnaire (IPAQ)

Changes in patient-reported weekly duration of total PA, assessed using the IPAQ (Expressed as metabolic equivalent (MET)-min per week: MET level x minutes of activity x events per week)

Changes in patient-reported signs of sarcopenia, assessed using The Strength, assistance in walking, rise from a chair, climb stairs, and falls (SARC-F) questionnaire (scale scoring: 0-10, the higher the score the better the condition)

Patient-reported symptomatic adverse events, assessed using the using the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

Changes in differential counts (total and per type: eosinofils, basofils, neutrofils, monocytes and lymphocytes)

Modifications of proteins after acute exercise. Muscle biopsies will be subjected to mass spectrometry-based proteomic analysis.

Modifications of mithochondrial regulation. Signaling of mitochondiral fission, fusion and mitophagy will be examined in mucle biopsies.

Inclusion Criteria: histologically verified, non-resectable cancer of the esophagus, stomach, or gastroesophageal junction referred to first line chemotherapy. Exclusion Criteria: Age < 18 Living outside the greater Copenhagen area Any other malignancy requiring active treatment Not eligible for chemotherapy Performance status > 2 Not able to swallow liquids Parenteral nutrition or enteral nutrition via feeding tube Physical or mental disabilities that prohibit execution of test or training procedures Pregnancy Inability to understand the Danish language