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.

Figure 1

Trial design. Available data (n) for each assessment method at week 9 is presented by study group.

Figure 2

Individual changes in muscle fibre size (cross sectional area). Waterfall plot: red bars represent individual reduction in fibre size (atrophy), blue bars represent individual increase in fibre size (hypertrophy). Note: overall, seven muscle biopsy samples (from different individuals) were of poor quality and were not valid for fibre size analysis, thus only 10 (CON), 9 (INT) and 12 (REF) individuals with evaluable baseline and week-9 biopsies are presented in this figure.

Figure 3

Within-group changes in secondary muscular end points. Random effect model-based within-group mean changes (s.e.m.) from baseline to week 9 based on all available data presented for (A) proportion of muscle fibre phenotypes: type I /type IIa/type IIx; (B) whole-body lean mass, (C) capillaries per fibre; (D) isometric quadriceps strength. * denotes within-group change significantly different from zero, P<0.05. Abbreviations: cap=capillaries; LBM=lean body mass.

Figure 4

Within-group changes in selected metabolic end points. Random effect model-based within-group mean changes (s.e.m.) from baseline to week 9 based on all available data presented for (A) plasma lipid concentrations: Total cholesterol/HDL cholesterol/LDL cholesterol/triglycerides; (B) fat mass/fat percentage. * denotes within-group change significantly different from zero, P<0.05. Abbreviations: HDL=high-density lipoprotein; LDL=low-density lipoprotein; pct=percentage; T-CHOL=total cholesterol; Tri=triglycerides.