Treatment-Related Fatigue


Clinical Background

Fatigue related to cancer and cancer treatment is one of the most common and distressing symptoms reported by cancer patients. Fatigue negatively impacts quality of life and in some cases may even influence a patients’ decision to continue treatment. Fatigue is characterized by a state of extreme tiredness that interferes with physical and mental functioning regardless of recent activity or rest.
There is currently an unmet need for effective therapies to treat fatigue. No pharmaceutical therapies are currently approved for fatigue. Stimulant medications have been met with limited success in clinical trials and are still in development.

Preclinical Models

Model Description Length Endpoints
Chemotherapy Induced Fatigue
Mice receive 2 cycles of doxorubicin treatment resulting in a reduction in voluntary wheel running activity 30 days Wheel running activity, additional behavioral test
Radiation Induced Fatigue
In development 30 days Wheel running activity, additional behavioral test

 

Chemotherapy Induced Fatigue

Biomodels has developed an animal model of chemotherapy related fatigue. In this model, fatigue is measured by analyzing daily wheel running activity. Mice will voluntarily run on a running wheel for the majority of the time spent awake, allowing for a reliable and consistent measure of activity with minimal manipulation of the animal. Following treatment with doxorubicin, the amount of wheel running activity is reduced close to half that of controls. This difference primarily occurs in the second half of the wake cycle (afternoon) and is independent of anemia. Interesting, clinically patients often report their fatigue as most severe in the afternoon. Overall, this model demonstrates face validity as a model of chemotherapy related fatigue and is useful for evaluating novel pharmaceuticals to treat the condition.

Daily Wheel Running Activity

Daily wheel running activity in untreated, control, and chemotherapy treated mice.

 

Circadian Rhythm of Activity

Circadian rhythm of wheel running activity. Note the reduction of activity in chemotherapy treated mice in the afternoon as compared to controls

 

Relevant Publications


Cancer-related Fatigue-mechanisms, Risk factors, and Treatments

Julienne E. Brower Nature Reviews Clinical Oncology 11,597–609 (2014)