Fatigue in palliative cancer care: are graded exercise and cognitive behaviour therapy effective treatments and what mediates the treatment response?

Since oncological treatments have been improved patients who are palliatively
treated for breast or colon cancer can live with cancer for years. Prolonging
patients* lives and preserving quality of life are the main aims of oncological
treatment. Quality of life is also an important parameter to determine whether
patients can continue with cancer treatment or start with further lines
treatment. Fatigue is an important symptom lowering the quality of life in
patients with advanced or metastatic cancer. From our own studies in patients
with advanced cancer we know fatigue is the most frequent reported symptom.
Patients reported fatigue even more often than pain, nausea and vomiting.
Furthermore, we found that nearly half of the palliative patients are severely
fatigued and that more severely fatigued patients report more disabilities.
Treating fatigue during the palliative trajectory is one of the unused
opportunities to improve the quality of life of patients with advanced cancer.
There is no evidence based intervention available for the treatment of severe
fatigue during the palliative trajectory. Sometimes palliative patients are
included in RCTs for fatigue but it remains unclear if this specific subgroup
of patients also benefited from the interventions.
Graded exercise therapy (GET) consisting of resistance and aerobic exercises,
and cognitive behaviour therapy (CBT) specifically designed for fatigue in the
palliative phase are two promising approaches to reduce fatigue, but the
effectiveness for cancer patients in the palliative trajectory has not been
demonstrated in controlled studies.
In the proposed project we will test the efficacy of both GET and CBT in a RCT
in reducing fatigue severity. Both interventions will be compared with usual
care.
GET and CBT assume different mechanisms in reducing fatigue. In GET it is
hypothesized that an increased level of physical fitness will reduce fatigue.
In CBT for fatigue it is assumed that a reduction in fatigue is mediated by a
change in fatigue related cognitions and that an increase in physical activity
which is one of the elements of CBT and concurrent improvement in physical
fitness, has no mediating role but acts as a catalysator for the change in
dysfunctional beliefs about fatigue. However, it could be that the expected
positive effect of GET and CBT is brought on by a change in both cognitions and
physical/activity fitness. In the proposed project we will test: a) if an
increased physical activity and/or fitness mediates the reduction in fatigue in
both GET and CBT; and/or b) test simultaneously if a change in fatigue related
cognitions, especially an increased self efficacy concerning fatigue and
reduced tendency to catastrophise in response to fatigue, mediates the fatigue
reduction in the two interventions. Identifying the mediating factors for both
interventions will enable us to improve interventions for fatigue in this
patient group.

Research questions
1. What are the effects of GET and CBT in severely fatigued patients receiving
first line of palliative treatment for breast or colon cancer on fatigue
severity compared to usual care?
2. What are the mediators of the change in fatigue brought on by GET and CBT?
More specifically, are (a) an increased level of physical activity and/or
physical fitness; or (b) a change in fatigue related cognitions, mediators for
the expected reduction in fatigue brought on by the two interventions?

Randomized, multi-centre controlled trial, with three conditions, i.e. one
control condition and two intervention conditions. Three hospitals will
participate in the study: the Radboud University Nijmegen Medical Centre,
Ziekenhuis Gelderse Vallei at Ede and Maxima Medisch Centrum at
Eindhoven/Veldhoven.

Condition 1: Graded exercise therapy: GET consisting of one weekly sessions of
two hours of resistance and aerobic training with a physical therapist during
12 weeks. GET will take place in small groups of maximal 5 patients.
Condition 2: Cognitive behaviour therapy (CBT): CBT consisting of eight
individual one-hour sessions with a therapist over a period of 12 weeks.

- There are risks involved in the physical exertion and exercise patients will
do in the GET condition. These will be limited by adapting the program to the
physical limitations of patients. Patients will also be screened by their
oncologist on their ability to do exercise. The burden is limited: doing
exercise and extra travelling for the 24 training sessions in 12 weeks.
Benefits: It is expected that severely fatigued palliative cancer patients will
benefit from GET. Their physical fitness will increase and their fatigue is
expected to decrease. We demonstrated this in a pilot study. This pilot study
also demonstrated that this specific form of GET was safe and patients were
positive about the intervention.
- There are no or only minimal risks involved in participating in the CBT
intervention. The burden is also limited and consists of extra travelling for
the sessions, following 8 sessions of CBT and doing home-work assignments. The
program is adapted to the physical limitations of the patients. There are
substantial potential benefits: CBT for fatigued cancer survivors proved to be
a highly effective intervention in reducing fatigue and disabilities and it is
likely that palliative cancer patients will also profit and become less
fatigued and disabled.
- All participants will do a 6-minute walking test to determine their physical
fitness at two assessments. This is not a maximal exercise test and therefore
poses only minimal risks for patients.
- Participants have to complete questionnaires, four times in a period of
approximately 6 months depending on the duration of the first line of
palliative cancer treatment. The questionnaires can be completed online or a
paper and pencil version will be send to the participant. It will take patients
about a half hour to complete the questionnaires. Completing the questionnaires
is without risks and the burden is limited.