Development of a mouse model for assessing fatigue during chemotherapy

Area of Science:

• Oncology
• Neuroscience
• Pharmacology

Background:

• Fatigue and sleep disturbances are prevalent in cancer patients, impacting quality of life and treatment adherence.
• Chemotherapy, especially neurotoxic agents like paclitaxel, can cause or exacerbate fatigue.
• Developing reliable models to assess chemotherapy-related fatigue is crucial for patient care.

Purpose of the Study:

• To establish a mouse model for evaluating chemotherapy-induced fatigue.
• To compare the fatigue-inducing and neurotoxic effects of paclitaxel and nab-paclitaxel.

Main Methods:

• Mice received either paclitaxel or nab-paclitaxel (10 mg/kg IV daily for 5 days).
• Activity, sleep, core body temperature, blood counts, cytokine levels, and neurological function were monitored.
• Assessments were conducted from one week before treatment up to four weeks after treatment.

Main Results:

• Both paclitaxel formulations caused significant activity disturbances during the first week post-treatment.
• Paclitaxel treatment resulted in more severe neutropenia and motor deficits compared to nab-paclitaxel.
• Neurological and activity deficits largely resolved by four weeks after treatment with either agent.

Conclusions:

• The studied measures effectively assess chemotherapy-related fatigue in a preclinical model.
• This model can differentiate the toxicity profiles of different chemotherapy formulations, such as paclitaxel and nab-paclitaxel.
• Nab-paclitaxel appears to have a more favorable side effect profile regarding neurotoxicity and fatigue compared to paclitaxel.