Safety and feasibility of high intensity interval training (HIIT) during cardiotoxic cancer treatment - ENTRANCE - a pilot study

Background

Anthracycline therapy remains a prevalent cause of cardiotoxicity, particularly among women undergoing treatment for breast cancer. This prospective randomized pilot study aims to assess the feasibility and safety of targeted high-intensity interval training (HIIT) for patients receiving cardiotoxic chemotherapy in oncology. The findings will provide a basis for future studies to explore the potential impact of HIIT on cardiovascular health and fitness in larger patient cohorts.

Methods

Participants with an initial diagnosis of early-stage breast cancer, for whom therapy included anthracyclines, were randomized into an intervention group (Arm A) or a control group (Arm B). Arm A completed an 8-week supervised high-intensity interval training (HIIT) program, integrated with their cancer treatment. The training involved twice-weekly sessions, each consisting of ten 60-second intervals at 85% of VO2peak, alternated with 120-second active recovery periods of unloaded pedaling at 50% VO2peak. Arm B received standard care, which included physiotherapy and exercise recommendations during consultations. Cardiovascular assessments—including ECG, transthoracic echocardiography (TTE), cardiopulmonary exercise testing (CPET), and endothelial function testing—were performed at baseline (T0), post-intervention (T1, 8 weeks), and following Paclitaxel treatment (T2). Primary endpoints for this pilot study were feasibility, training adherence, and the incidence of training-related cardiovascular events.

Results

To date, 18 female patients (mean age 49.7 ± 11.7 years, BMI 27.1 ± 5.8) have been enrolled in the study. None had a history of cardiovascular disease. Based on the HFA ICOS score, 15/18 patients were classified as low risk, 2/18 as moderate risk (due to age > 65years), and 1/18 as high risk (due to prior anthracycline therapy). Patients were randomized into either the intervention group (10 patients) or the control group (8 patients). Two patients, one from each group, withdrew due to travel distance. Of the remaining 9/10 participants in the intervention group, all completed the training with a mean adherence rate of 75.9 ± 13.9%. There were no cardiovascular events related to the HIIT.

Baseline ejection fraction (EF) was 59.8 ± 3.6%, and global longitudinal strain (GLS) was -20.9 ± 2.9%, with no significant differences between the groups at baseline (p=0.171 for EF, p=0.573 for GLS). These values remained stable after the intervention at T1 (EF +1.7 [-1.5 to +6.6] vs -2.0 [-1.2 to +1.2], p=0.332). However, by T2, one case of mild cancer-related cardiac dysfunction was observed in the high-risk patient within Arm A.

Peak VO2 did not change in the HIIT group from baseline to post-chemotherapy (T1) (+0.25 [-0.9 to +3.3] mL/kg/min, p=0.89). However, a trend toward decreased peak VO2 was observed in the control group (-3.8 [+0.625 to -8.2] mL/kg/min, p=0.068).

Conclusion

This pilot study demonstrates that HIIT, combined with comprehensive cardiovascular assessment, is both safe and feasible, with high adherence rates, even for patients undergoing frequent anthracycline-based chemotherapy. A subsequent larger cohort study is needed to evaluate the potential impact of HIIT on cardiovascular health and fitness during cancer treatment.