Cancer related fatigue is a distressing, persistent, subjective sense of exhaustion related to the cancer or to its treatment, not proportional with the current commitments and impacting on the usual functions. Differently from the fatigue of healthy individuals, cancer related fatigue is not alleviated by sleep or rest. The incidence of cancer related fatigue is impressive because it’s present in about 40% at diagnosis, in about 80-90% in patients admitted to chemotherapy and radiotherapy and varying from 20-50% of patients after the end of any treatment for the cancer. This is the most important problem. In the elderly overall the incidence of cancer related fatigue is about 70%.
Before speaking about the treatment of cancer related fatigue it’s important to identify and possibly remove the predisposing factors that are related to cancer complications, for example anaemia, for example hypocalcaemia; related to physical side effects of cancer or cancer treatment, for example pain, dyspnoea; to comorbid conditions such as hypothyroidism, such as diabetes; to psychological factors such as insomnia, anxiety, depression; to side effects of other drugs used by the people such as opioids or psychiatric drugs, and finally to heterogenetic problems related to the chemotherapy, hormone therapy, radiotherapy, immunotherapy and so on.
When you would like to speak about treatment in these patients we need to distinguish pharmacological treatments from non-pharmacological treatments. Pharmacological treatments are constituted by psychostimulants, for example methylphenidate or modafinil. Unfortunately with the available studies on 19 randomised double-blind studies having cancer related fatigue as a primary endpoint 15 are negative studies. Therefore the use of the psychostimulants in clinical practice is discussable because their efficacy is not clearly demonstrated. We have other classes of drugs, for example antidepressants, for example acetylcholinesterase inhibitors. All the studies with these classes of drugs are negative; the only drug useful, but only in the setting of advanced cancer disease, are corticosteroids and if you want to administer dexamethasone you need to use 4mg twice a day for more and more days to come back to fight against cancer related fatigue.
Concerning the non-pharmacological intervention we need to distinguish physical exercise, psycho-educational intervention and mind-body intervention. These types of treatments are effective, especially in the phase when the patient is over the cancer treatment, after the cancer treatment. Physical exercise is suggested, recommended by different organisations, for example, 150 minutes of moderate aerobic exercise during a week plus three or two sessions of strength training but this all indicated in which there are no contraindications. Other important interventions, non-pharmacological, are psycho-educational interventions or cognitive behavioural therapy; this has been demonstrated effective in several randomised controlled trials. Finally, the mind-body interventions are represented by different things, for example ginseng that has been demonstrated efficacious in a large study, for example yoga, for example acupuncture, but these two interventions can require again new data to demonstrate their efficacy and some mind-body interventions such as massage, rehabilitation, touch therapy and so on.
Should there be more trials examining quality of life?
We need more and more trials to demonstrate the role of non-pharmacological treatments because these are very important because done in patients with long cancer survival and this is a good clinical condition but cancer related fatigue is having an important impact on the quality of life of these patients. In other settings the drugs unfortunately have not such big importance but we need to have more and more studies to identify the neurotransmitters involved in the cancer related fatigue.
Is there anything that can be done in the short term to improve quality of life?
Some people try to combine the pharmaceutical treatments with the non-pharmaceutical intervention but at the present these are experimental attempts to combat against cancer related fatigue. Until now generally they are independent trials, only on a few occasions with preliminary studies this combination has been evaluated. The results seem promising but we need randomised clinical trials of course.
What would be the long-term positive effects of these trials?
Some non-pharmacological treatments should be put into routine clinical practice, for example physical exercise. This is not considered often in our suggestions but it is very important because it can resolve the problems of cancer related fatigue, especially in long-term survivors. In other situations, for example acupuncture, we have a lot of studies on acupuncture but there are in many of these studies a lot of possible biases that cannot permit us to draw firm conclusions about these studies. Therefore, improving the methodology of the trials that we can carry out, we can improve the results and the possibility to identify the really efficacious interventions.
What needs to be done and what is the key message you would like to impart?
The message is that we need to improve, to put more and more attention to the cancer related fatigue because this is the top of the distressing side effects of treatment or of the cancer patient. Therefore, when we see the patient for the first time in our laboratory we need to ask the patients about the presence or not of fatigue and if so we need to know the intensity of fatigue and to discuss with the patients the possible treatment.
