Aims: High attrition rate in clinical trials causes selection bias and reduces the validity of outcome data. Our aim was to identify metabolic and clinical characteristics of subjects who dropped out of a prospective nutrition trial during chemotherapy.
Methods: In 16 subjects with solid tumours undergoing chemotherapy, we assessed fasted whole body net protein breakdown (PB), myofibrillar PB (MPB) and Glycine (GLY) production rates by pulse IV administration of stable tracers: 2H3-Leucine (LEU), [2H3]tau-methylhistidine and 2H2-GLY, prior to the start of a 10 week nutritional trial. Furthermore, we measured net protein synthesis (netPS) and protein digestion capacity (PD) after oral intake of a high-protein meal with added [1-13C]PHE and 15N-spirulina, and primed continuous IV infusion of [ring-2H5]PHE and [13C9-15N]TYR. We assessed FFM-i (DXA), muscle strength (handgrip-, inspiratory-, and leg), endurance, protein intake, physical activity, quality of life (EORTC-QLQc30). Amino acid concentrations/enrichments by LC-MS/MS, and statistics by unpaired t-tests and spearman correlation tests.
Results: Seven subjects dropped out within 10 weeks of follow-up. Fasted PB, MPB, GLY production rate, netPS after meal intake, PD, age, FFM-i and muscle strength were comparable between dropout and non-dropout subjects. Dropouts had a lower handgrip endurance (31.0±9.2% vs. 17.7±12.9% strength lost, p=0.005), protein intake (1.4±0.7 vs. 0.7±0.4 g/kg/d, p=0.06), physical activity (62.4±53.0 vs. 191.4±92.6, p=0.006) and global health status (46.4±19.8 vs. 74.1±12.8, p=0.004) and more appetite loss (52.4±42.4 vs. 11.1±23.6, p=0.03).
Conclusions: Subjects undergoing chemotherapy who drop out of a clinical trial report a lower dietary protein intake, physical activity, appetite and quality of life. This information can be valuable for future cancer trials to identify subjects with a high chance to drop out.