The mechanisms that cause or promote fatigue in
patients with cancer still are understood poorly and
have been the subject of several theories.14 One of the
major obstacles to basic and preclinical research has
been the problematic development of animal models
of CRF due to the inherent subjectivity of the symptom
and the difficulty of establishing objective, behavioral
correlates of fatigue. Voluntary, motivated activity
has been proposed as one such correlate in
animals
In addition to the direct effects of cancer and the
various modes of cancer treatment, a wide variety of
other phenomena contribute to fatigue in cancer patients
(Table 1). Proposed tumor-related factors include
abnormalities of energy metabolism, decreased
availability of metabolic substrates, abnormal production
of substances inhibiting metabolism or normal
muscle function, neurophysiologic changes of skeletal
muscles, chronic stress response, and hormonal
changes
Although an increased energy expenditure traditionally
has been regarded as a characteristic metabolic
abnormality of cancer patients, carefully conducted investigations describe a heterogeneous
picture, with resting energy expenditure varying between
60% than predicted and 150% than predicted.16,17
It has been hypothesized that, whereas
resting energy expenditure is increased, total energy
expenditure may be unchanged due to a fall in physical
activity.18 This model, however, fails to elucidate
how decreased physical activity leads to the perception
of fatigue.