Christensen, Jesper Frank3; Jones, L W11; Tolver, Anders12; Jørgensen, L W5; Andersen, J.L.6; Adamsen, L7; Højman, P.8; Nielsen, R. H.9; Rørth, Mikkel10; Daugaard, Gedske13
1 Department of Mathematical Sciences, Faculty of Science, Københavns Universitet2 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet3 The University Hospitals Centre for Health Care Research (UCSF), Copenhagen University Hospital , Copenhagen4 Memorial Sloan-Kettering Cancer Center5 The University Hospitals Centre for Health Research (UCSF), Copenhagen, Denmark6 Bispebjerg University Hospital7 The University Hospitals Centre for Health Research, Copenhagen University Hospital, Copenhagen8 Department of Oncology, Rigshospitalet9 Copenhagen University Hospital Bispebjerg10 Copenhagen University Hospital, Rigshospitalet11 Memorial Sloan-Kettering Cancer Center12 Department of Mathematical Sciences, Faculty of Science, Københavns Universitet13 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet
a randomized controlled trial
Abstract Background: Bleomycin–etoposid–cisplatin (BEP) chemotherapy is curative in most patients with disseminated germ cell cancer (GCC) but also associated with toxic actions and dysfunction in non-targeted tissues. We investigated changes in muscle function during BEP and the safety and efficacy of resistance training to modulate these changes. Methods: Thirty GCC patients were randomly assigned to resistance training (resistance training group (INT), n=15) or usual care (CON, n=15) during 9 weeks of BEP therapy. Resistance training consisted of thrice weekly sessions of four exercises, 3–4 sets/exercise of 10–15 repetitions at 12–15 repetition maximum load. The primary endpoint was muscle fibre size, assessed in muscle biopsies from musculus vastus lateralis. Secondary endpoints were fibre phenotype composition, body composition, strength, blood biochemistry and patient-reported endpoints. Healthy age-matched subjects (REF, n=19) performed the same RT-programme for comparison purposes. Results: Muscle fibre size decreased by −322 μm2 (95% confidence interval (CI): −899 to 255; P=0.473) in the CON-group and increased by +206 μm2 (95% CI: −384 to 796; P=0.257) in the INT-group (adjusted mean difference (AMD), +625 μm2, 95% CI: −253 to 1503, P=0.149). Mean differences in type II fibre size (AMD, +823 μm2, P=0.09) and lean mass (AMD, +1.49 kg, P=0.07) in favour of the INT-group approached significance. The REF-group improved all muscular endpoints and had significantly superior changes compared with the INT-group (P<0.05). Conclusions: BEP was associated with significant reduction in lean mass and strength and trends toward unfavourable changes in muscle fibre size and phenotype composition. Resistance training was safe and attenuated dysfunction in selected endpoints, but BEP blunted several positive adaptations observed in healthy controls. Thus, our study does not support the general application of resistance training in this setting but larger-scaled trials are required to confirm this finding.