title: Safety and efficacy of resistance training in germ cell cancer patients undergoing chemotherapy: 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 μm(2) (95% confidence interval (CI): -899 to 255; P=0.473) in the CON-group and increased by +206 μm(2) (95% CI: -384 to 796; P=0.257) in the INT-group (adjusted mean difference (AMD), +625 μm(2), 95% CI: -253 to 1503, P=0.149). Mean differences in type II fibre size (AMD, +823 μm(2), 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.
authors.affiliation: 1] University Hospitals Centre for Health Research, Rigshospitalet, DK 2100 Copenhagen, Denmark [2] Department of Oncology, Rigshospitalet, DK 2100 Copenhagen, Denmark.
authors.forename: J F
authors.initials: JF
authors.lastname: Christensen
authors.affiliation: Memorial Sloan-Kettering Cancer Center, Department of Cardiology, New York, NY 10065, USA.
authors.forename: L W
authors.initials: LW
authors.lastname: Jones
authors.affiliation: Department of Mathematical Sciences, University of Copenhagen, DK 2100 Copenhagen, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Tolver
authors.affiliation: University Hospitals Centre for Health Research, Rigshospitalet, DK 2100 Copenhagen, Denmark.
authors.forename: L W
authors.initials: LW
authors.lastname: Jørgensen
authors.affiliation: 1] Institute of Sports Medicine Copenhagen, Department of Orthopaedic Surgery, Bispebjerg Hospital, DK 2400 Copenhagen, Denmark [2] Centre for Healthy Ageing, Faculty of Health Sciences, University of Copenhagen, DK 2100 Copenhagen, Denmark.
authors.forename: J L
authors.initials: JL
authors.lastname: Andersen
authors.affiliation: University Hospitals Centre for Health Research, Rigshospitalet, DK 2100 Copenhagen, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Adamsen
authors.affiliation: Research Centre of Inflammation and Metabolism, Rigshospitalet, DK 2100 Copenhagen, Denmark.
authors.forename: P
authors.initials: P
authors.lastname: Højman
authors.affiliation: 1] Institute of Sports Medicine Copenhagen, Department of Orthopaedic Surgery, Bispebjerg Hospital, DK 2400 Copenhagen, Denmark [2] Centre for Healthy Ageing, Faculty of Health Sciences, University of Copenhagen, DK 2100 Copenhagen, Denmark.
authors.forename: R H
authors.initials: RH
authors.lastname: Nielsen
authors.affiliation: 1] University Hospitals Centre for Health Research, Rigshospitalet, DK 2100 Copenhagen, Denmark [2] Department of Oncology, Rigshospitalet, DK 2100 Copenhagen, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Rørth
authors.affiliation: Department of Oncology, Rigshospitalet, DK 2100 Copenhagen, Denmark.
authors.forename: G
authors.initials: G
authors.lastname: Daugaard
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000503:physiopathology; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy / Q000503:physiopathology / Q000628:therapy*; D011446:Prospective Studies; D055070:Resistance Training / Q000009:adverse effects* / Q000379:methods*; D016037:Single-Blind Method; D013736:Testicular Neoplasms / Q000188:drug therapy / Q000503:physiopathology / Q000628:therapy*
chemical_list: D001761:Bleomycin; D005047:Etoposide; D002945:Cisplatin