Impact of Aerobic Exercise on Immune Response and Side Effects of Cancer Treatments
Condition: Colorectal Cancer Stage IV
MeSH terms: Colorectal Neoplasms
Study type: Interventional

Summary: 
      Aerobic exercise is associated with many benefits in patients with cancer treatments. Among
      these, the reduction of cancer-related fatigue (CRF) is one of the best demonstrated.
      Besides, several animal models have shown a marked reduction in tumor growth with aerobic
      exercise, sometimes by more than 60%. As the level of physical activity is convincingly
      associated with a reduction in the risk of cancer or recurrences, this suggests that aerobic
      exercise may represent a central therapeutic approach during treatment, both against CRF and
      for its potential anti-tumor effect.

      Both benefits have been suggested to be based on the immunostimulatory and anti-inflammatory
      effects of exercise. Indeed, systemic inflammatory activity seems to play a central role in
      the etiology of CRF during cancer treatments, among other things by stimulating the
      neuro-inflammatory activity of the central nervous system. Also, regarding the anti-tumor
      effect of exercise, animal models show that this benefit is partly explained by an increase
      in the activity of immune cells called natural killers (Natural Killer; NK) in tumor tissue
      and a reduction in the activity of regulatory T cells, the latter having an immunosuppressive
      effect. However, in humans, the results vary. While some improvement in NK cell activity has
      been reported in response to aerobic training in breast cancer survivors, others have seen no
      effect on the immune profile of patients and survivors. On the other hand, some authors
      report an improvement in the inflammatory profile with training, while others report little
      or no effect, as well as weak associations with the perception of fatigue.

      Although these results seem to discredit the hypothesis of immune and inflammatory regulation
      of exercise in humans, these studies have all looked at the effect of several weeks of
      training on the inflammatory and immune profile on an empty stomach and rest. However,
      several results from the field of exercise immunology convincingly show that the
      anti-inflammatory effect, as well as the immunostimulating effect of aerobic exercise
      (including the anti-tumor activity of NK cells) are mainly acute and transient, ie. in the
      hours following the end of the effort. Furthermore, certain results suggest that in the
      context of chemotherapy treatments, cyclical treatment by nature, the peaks of fatigue are
      also acute (i.e. in the days following the treatment) and parallel to peaks of inflammatory
      activity.

      Considering these results, it is therefore plausible to assume that the effect of aerobic
      exercise on suppressing tumor growth and reducing CRF results rather than the repetition of
      this acute response at each exercise session. In this case, the prescription of aerobic
      exercise preceding a session of chemotherapy could potentially represent an interesting
      therapeutic modality, allowing both the reduction of the CRF associated with this treatment,
      as well as a better response to the treatment. Besides, as this acute response seems to be
      highly dependent on the intensity of the effort, high-intensity interval training (HIIT)
      could be a particularly interesting approach in this context, because it does not require
      that the high intensity or long-lasting exercise. However, considering the immunosuppressive
      and pro-inflammatory effects of chemotherapy, the extent of the acute response to exercise
      may not allow this type of therapeutic use to be considered in this population. To date, no
      study has attempted to characterize the acute immune and inflammatory response following
      aerobic exercise in patients currently undergoing chemotherapy treatments.
    


Intervention name(s): Resting state (Control); Moderate Intensity Continuous Exercise (MICE); High Intensity Interval Exercise (HIIE)
Intervention type(s): Other; Other; Other
Intervention description(s): Participants were asking to sit on a sofa for 50 minutes.; MICE condition consisted of 50 minutes of moderate and continuous aerobic exercise on ergocycle. This includes a warm-up and cool-down period at low intensity, and a 40-minute period at moderate intensity (power output is equivalent to an effort perception from 4 to 6/10 and lactate levels from 2 to 4 mmol/L, obtained by submaximal test); HIIT condition consisted of a 30 minutes of aerobic exercise training perform on ergocycle. This includes a warm-up at low intensity, followed by 10 blocks of 1 minute at high intensity (power output corresponding to the highest power reached at the submaximal test and lactate levels > 4 mmol/L) and 1 minute of active cooldown (effort perception around 1-2/10).
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Each participant performed 3 experimental conditions (rest, moderate continuous training and interval training).
Masking: None (Open Label)
Primary purpose: Supportive Care