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Table 3 – Summary of clinical findings in trials examining exercise intervention for doxorubicin-mediated cardiotoxicity. Positive findings may predict similar success in trastuzumab-mediated cardiotoxicity given some mechanistic overlap between the two drugs

From: Mechanisms of trastuzumab induced cardiotoxicity – is exercise a potential treatment?

Reference

Patient Group

Intervention

Finding

Kirkham et al., 2018 [62]

24 patients received (intervention group = 13) 60 mg/m2 of Dox and 600 mg/m2 of cyclophosphamide

24-48 h before each patient’s first doxorubicin treatment

Supervised treadmill bout involving 10-min warm-up, 30 min (70% age-predicted HRR), 5 min cooldown

No difference in longitudinal strain, twist or cardiac troponin

Mitigated increase in cardiac output, resting heart rate and decreased systemic vascular resistance relative to control group

Lee et al., 2019 [63]

30 participants (intervention group = 15) following completion of 8-week anthracycline-based chemotherapy (every 2-weeks for 4 cycles)

3x weekly for 8 weeks

HIIT sessions included 7 × (1-min interval 90% peak power output (PPO) followed by 2 min interval at 10% PPO)

VO2-max maintained in HIIT groups compared with significant decrease in control group

Mijwel et al., 2018 [64]

59 participants scheduled to undergo chemotherapy consisting of anthracyclines

Resistance training (RT) group = 30

Aerobic training (AT) group = 27

2x weekly, 16 weeks

RT = 2–3 sets of 8–12 reps at 80% of 1-rep-max

AT = 20 min of moderate-intensity continuous aerobic exercise

RT and AT significantly attenuated the fall in predicted VO2peak seen in control groups

Ma, 2018 [65]

70 participants (intervention group = 31) undergoing anthracycline-containing therapy

Aerobic exercise 3x weekly for 16 weeks

Significant attenuation of LVEF decline in exercise group relative to control group

Foulkes et al., 2022 [54]

104 participants (intervention group = 52)

60 mg/m2 doxorubicin combined with 600 mg/m2 cyclophosphamide for 4 cycles (3 months)

3-4x weekly for 12 months

Broken into 3 phases with decreasing levels of supervision

Progressive loading/de-loading of volume in line with chemotherapy cycles

Sessions consisted of varying combinations of moderate-intensity endurance training (30-60 min at heart rate [HR] 5–30 b/min below ventilatory threshold) ), tempo training (35 min at HR within 10 b/min of VT), high intensity interval training (4 × 2–4 min at > 85% maximal HR), and moderate-to-high intensity resistance training (2 sets x 8–15 repetitions at load equivalent to 60–85% of 1-repetition max)

Exercise associated with a net + 3.5 mL/kg/min improvement in VO2 peak

Significantly greater improvements in cardiac reserve measures (change in CO, SV, LVEF and RVEF from rest to peak exercise)