Discussion
testicular cancer, fatigue, pulmonary toxicity, vascular endothelial dysfunction
ENDOTHELIAL DYSFUNCTION, ADVERSE EVENTS, EVENT, EVENTS, ADVERSE EFFECTS, TESTICULAR CANCER, INFLAMMATORY RESPONSE
In this exploratory subgroup analysis of the ACT-trial, we found beneficial effects of a physical exercise intervention initiated during compared to after BEP-chemotherapy on pulmonary function parameters and markers of endothelial dysfunction in patients with metastatic testicular cancer. We found statistically significant differences between groups for FVC, FEV1, DLCO, KCO, vWF and factor VIII, measured directly post-chemotherapy in favour of the group that exercised during chemotherapy (group A). Also, 1-year post-intervention, significant differences were found in pulmonary function (KCO, DLCO) in favour of group A.Physical exercise may reduce the BEP-induced generation of reactive oxygen species and thereby prevent the development of vascular endothelial dysfunction and the consequent inflammatory response (Simioni et al. We also found that FEV1 and FVC were better preserved during chemotherapy in group A compared to group B. The physical exercise intervention during BEP-chemotherapy may maintain physical fitness and respiratory muscle strength and thereby possibly preserved values of FEV1 and FVC (Kenn et al. Results of the present study suggest that attending physical exercise during BEP-chemotherapy might protect against vascular endothelial dysfunction. Currently, limited data are available on effects of exercise on vascular endothelial dysfunction. A retrospective study in elderly male volunteers showed a significant inverse dose–response relationship between physical exercise and fibrinogen levels, factor VIII, vWF, t-Pa and PAI-1 (Wannamethee et al. In total, 3 out of 30 patients (10.0%, non-significant), all in group A, developed signs of bleomycin-induced pulmonary toxicity. Two out of 30 patients (13.3%, non-significant), all in group B, developed a vascular event. However, the small numbers make it difficult to draw conclusions about the clinical significance and importance of this finding. Future studies including larger patient cohorts attending physical exercise during and after BEP-chemotherapy, should monitor the occurrence of bleomycin-induced pulmonary toxicity and occurrence of vascular events.No adverse events related to the exercise intervention occurred in our study. In a study in which patients with testicular cancer were randomized to supervised high-intensity interval training (HIIT, 85–95% of HRComparison of the effects of exercise on treatment-related morbidity to a control group would have been very interesting. However, when the study protocol of the ACT-trial was written (2012), it was already known that physical exercise during and after treatment with chemotherapy has evident beneficial effects on various chemotherapy-related adverse effects, and that physical training was beneficial on several outcomes such as physical fitness, muscle strength, fatigue, and quality of life. In addition, exercise programs appeared to be safe. However, knowledge of the timing of the physical exercise training was lacking and therefore, the topic of this study was randomizing exercise during versus after chemotherapy.To our knowledge, this is the first study showing beneficial effects of physical exercise during BEP-chemotherapy on pulmonary function parameters and markers of vascular endothelial activation in patients with testicular cancer. The study had several strengths and limitations. Strengths are the randomized design and the high adherence rate to the physical exercise intervention. Limitations are the small patient groups and the lack of importance of DLCO in predicting bleomycin-induced pulmonary toxicity (Watson et al. 