Solheim 2017.

Study characteristics
Methods	Study design: randomised controlled trial, parallel, multicentre, open‐label Study dates: July 2011 to April 2014 Countries: Norway, the UK
Participants	Total participants: 44 Inclusion criteria: aged 18–80 years; stage III/IV non‐small cell lung cancer or inoperable pancreatic cancer; due to commence chemotherapy; Karnofsky Performance Status > 70; no contraindication to the study interventions (primarily the anti‐inflammatory medication); body mass index < 30 kg/m2; and < 20% weight loss in the previous 6 months Exclusion criteria: received systemic anticancer therapy in the preceding 4 weeks; taking regular oral steroid medication; participating in other interventional clinical trials or who within 30 days prior to inclusion were taking other agents for the prevention or treatment of cachexia (e.g. megestrol acetate, progestational agents, growth hormone, dronabinol, marijuana or other anabolic agent); with renal impairment defined as creatinine clearance < 30 mL/minute; with potential contraindications to celecoxib (New York Heart Association Functional class III or IV heart failure, uncontrolled hypertension (diastolic blood pressure > 95 mmHg at screening), history of previous myocardial infarction, unstable angina, coronary revascularisation, uncontrolled arrhythmia, cerebrovascular accident, previous gastrointestinal inflammatory disease and history of gastrointestinal ulceration, history of bronchospasm, asthma, rhinitis, nasal polyps, angioneurotic oedema or urticaria with intake of NSAID or aspirin therapy, history of hypersensibility related to intake of acetylsalicylic acid or NSAIDs) Participants characteristics: Gender (men/women) · Experimental intervention group: 15/10 · Comparator intervention group: 11/10 Age (years) (median, interquartile range) · Experimental intervention group: 63.0, 54.5–68.0 · Comparator intervention group: 59.0, 52.5–67.0 Race/Ethnicity (caucasian/other) · Experimental intervention group: 24/1 · Comparator intervention group: 21/0 Weight (kg) (mean ± SD) · Experimental intervention group: 70.18 ± 13.03 · Comparator intervention group: 66.63 ± 10.46 BMI (kg/m2) (median, interquartile range) · Experimental intervention group: 24.2, 21.4–27.0 · Comparator intervention group: 24.0, 21.9–25.3 Type of cancer (non‐small cell lung cancer/pancreatic) · Experimental intervention group: 15/10 · Comparator intervention group: 11/10 Cancer staging (Karnofsky performance status) (median, interquartile range) · Experimental intervention group: 90.0, 80.0–100.0 · Comparator intervention group: 90.0, 80.0–90.0 Stage of cachexia (% of weight loss in the previous 6 months) (median, interquartile range) · Experimental intervention group: 5.7, 0.6–13.3 · Comparator intervention group: 5.4, 1.6–11.7 Comorbidities · Experimental intervention group: not reported · Comparator intervention group: not reported
Interventions	Experimental group Celecoxib 300 mg once daily 2 × 220 mL cartons of ONS (ProSure Abbott) (each carton contains 1 g EPA), giving a net intake of 2 g/day Nutritional counselling with advice on optimisation of nutritional intake that was provided by a dietician or trial nursing staff (or both). A nutritional interview (30 minutes) was performed at baseline, and then participants received oral and written advice on improving energy and protein intake. Typically, the advice was to increase meal frequency and use energy‐dense foods Exercise programme including home‐based aerobic and resistance training devised by a physiotherapist. The aerobic component consisted of 30 minutes of aerobic exercise of the participant's choice twice a week. The resistance exercise component consisted of 6 individualised exercises that follow the same schedule, targeting major muscle groups in the upper body and legs, to be performed 3 times weekly for about 20 minutes. The exercises consisted of push‐ups against the wall, overhead presses and bicep curls and, for the legs, squats, lunges and calf raises using weights Participants were contacted a minimum of once a week (maximum of twice) by telephone to assess compliance and to encourage adherence to the multimodal intervention Type of exercise: aerobic and resistance individualised training Duration of exercise programme: 3 months Intensity of exercise: not reported Frequency of exercise (day/week): aerobic/resistance training: 2/3 Volume of exercise (minutes/day): aerobic/resistance training: 30/20 Supervision: physiotherapist Setting: home‐based Comparator group: usual care without exercise intervention. They were asked to keep their everyday habits without changing daily physical activity level. Nutritional support by a professional dietician was only provided when so‐called medically indicated (as judged by the treating physician) Concomitant interventions: regular oncology review: outpatient appointments prior to chemotherapy (prechemotherapy assessments) and hospital visits (single day) for chemotherapy delivery (most commonly every 3 weeks). The most common chemotherapy regimens were Folfirinox (folinic acid, 5‐fluorouracil, irinotecan and oxaliplatin), vinorelbine‐carboplatin/cisplatin, gemcitabine mono, and pemetrexed‐carboplatin/cisplatin. All participants had their symptoms managed according to guidelines at each centre. Follow‐up: 6 weeks
Outcomes	Primary outcomes Feasibility How measured: assessed by proportion of participants screened vs those consented and attrition rates. In cancer trials, the percentage of participants recruited vs those screened varies: we accepted 10% recruitment and an attrition rate of < 26% as feasible Time points measured: 6 weeks Secondary outcomes Bodyweight How measured: not reported Time points measured: baseline, 6 weeks Body mass index How measured: not reported Time points measured: baseline, 6 weeks Muscle mass (muscle surface area, cm2) How measured: computed tomography Time points measured: baseline, 6 weeks Adherence to prescribed exercise programmes How measured: self‐reported compliance Time points measured: baseline, 6 weeks Muscle strength How measured: hand‐held dynamometer assessing grip strength Time points measured: baseline, 6 weeks Physical function How measured: number of steps using ActivPAL (physical activity meter worn for 7 days and 6MWT) Time points measured: baseline, 6 weeks Nutritional status How measured: aPG‐SGA Time points measured: baseline, 6 weeks Nutritional intake How measured: 10‐point verbal scale assessment of nutritional intake (AveS) Time points measured: baseline, 6 weeks Fatigue How measured: Fatigue Severity Scale Time points measured: baseline, 6 weeks Safety and survival How measured: Fatigue Severity Scale Time points measured: baseline, 6 weeks
Notes	1 author received research funding from pharmaceutical industry (Abbott Laboratories). The oral nutritional supplements (ONS; ProSure) was received free of charge from Abbott Nutrition, a subsidiary company of Abbott Laboratories. Participants were recruited from 3 centres of 2 countries: Norway St. Olav's Hospital, Trondheim University Hospital Oslo University Hospital, Ullevål UK Beatson West of Scotland Cancer Centre, Glasgow
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "A web‐based randomisation system developed and administered by a research centre were undertaken in a 1:1 ratio with stratification by centre and tumour type."
Allocation concealment (selection bias)	Low risk	Quote: "administered by a research centre."
Blinding of participants and personnel (performance bias) All outcomes	High risk	Quote: "This unblinded design."
Blinding of outcome assessment (detection bias) All outcomes	High risk	Quote: "This unblinded design."
Incomplete outcome data (attrition bias) All outcomes	Low risk	There were losses to follow‐up described in the study. 2 participants died (1 in each group). For 'endurance', > 50% losses occurred. Intention to treat used do adjust losses of follow‐up.
Selective reporting (reporting bias)	High risk	Exclusion criteria were not reported in protocol. There were differences between the 2 publications for this study. Lack of reporting at all follow‐ups time points.
Other bias	Low risk	No other bias found.

6MWT: six‐minute walk test; aPG‐SGA: abridged Patient Generated Subjective Global Assessment; AveS: Analogue verbal scale; CES‐D: Center for Epidemiological Studies Depression Scale; EPA: eicosapentaenoic acid; FAACT: Functional Assessment of Anorexia/Cachexia Therapy; FACT‐An: The Functional Assessment of Cancer Therapy‐Anemia; FHNSI‐22: Functional Assessment of Cancer Therapy Head/Neck Symptom Index‐22; MFI: Multidimensional Fatigue Inventory; NSAID: non‐steroidal anti‐inflammatory drug; PG‐SGA: Patient Generated‐Subjective Global Assessment; RM: repetition maximum; RPE: rating of perceived exertion.