Effects and tolerability of exercise therapy modality on cardiorespiratory fitness in lung cancer: a randomized controlled trial

Abstract

Background: Poor cardiorespiratory fitness (CRF) is a cardinal feature of post-treatment primary lung cancer. The most effective exercise therapy regimen to improve CRF has not been determined.

Methods: In this parallel-group factorial randomized controlled trial, lung cancer survivors with poor CRF (below age-sex sedentary values) were randomly allocated to receive 48 consecutive supervised sessions thrice weekly of (i) aerobic training (AT)-cycle ergometry at 55% to >95% of peak oxygen consumption (VO₂ peak); (ii) resistance training (RT)-lower and upper extremity exercises at 50-85% of maximal strength; (iii) combination training (CT)-AT plus RT; or (iv) stretching attention control (AC) for 16 weeks. The primary endpoint was change in CRF (VO₂ peak, mL O₂ ·kg^-1 ·min^-1 ). Secondary endpoints were body composition, muscle strength, patient-reported outcomes, tolerability (relative dose intensity of exercise), and safety. Analysis of covariance determined change in primary and secondary endpoints from baseline to post-intervention (Week 17) with adjustment for baseline values of the endpoint and other relevant clinical covariates.

Results: Ninety patients (65 ± 9 years; 66% female) were randomized (AT, n = 24; RT, n = 23; CT, n = 20; and AC, n = 23) of the planned n = 160. No serious adverse events were observed. For the overall cohort, the lost-to-follow-up rate was 10%. Mean attendance was ≥75% in all groups. In intention-to-treat analysis, VO₂ peak increased 1.1 mL O₂ ·kg^-1 ·min^-1 [95% confidence interval (CI): 0.0, 2.2, P = 0.04] and 1.4 mL O₂ ·kg^-1 ·min^-1 (95% CI: 0.2, 2.5, P = 0.02) in AT and CT, respectively, compared with AC. There was no difference in VO₂ peak change between RT and AC (-0.1 mL O₂ ·kg^-1 ·min^-1 , 95% CI: -1.2, 1.0, P = 0.88). Favourable improvements in maximal strength and body composition were observed in RT and CT groups compared with AT and AC groups (Ps < 0.05). No between-group changes were observed for any patient-reported outcomes. Relative dose intensity of exercise was lower in RT and CT compared with AT (Ps < 0.05).

Conclusions: In the context of a smaller than planned sample size, AT and CT significantly improved VO₂ peak in lung cancer survivors; however, the tolerability-to-benefit ratio was superior for AT and hence may be the preferred modality to target impaired CRF in post-treatment lung cancer survivors.

Trial registration: ClinicalTrials.gov NCT01068210.

Keywords: Aerobic training; Cancer survivorship; Combination training; Exercise capacity; Resistance training.

Figure 1

F CONSORT flow for non‐pharmacological trials.

Figure 2

Waterfall plots for change in cardiorespiratory fitness. The technical error for VO₂peak (Δ1.12 mL O₂·kg⁻¹·min⁻¹) is illustrated by the shaded area. A change in cardiorespiratory fitness greater than technical error is classified as a meaningful response. AC, attention control; AT, aerobic training; CT, combination training; RT, resistance training.