Colorectal cancer is 37% higher in the North West than the national average and is treated by chemotherapy, including fluorouracil, capecitabine, and oxaliplatin. A side effect of these drugs is loss of memory, forgetfulness, and general brain fog, which can persist for months after the end of treatment. These symptoms are collectively known as 'chemo-brain'. An existing prehabilitation intervention that has been previously developed will be used, which increases fitness and reduces hospital length of stay in colorectal cancer surgery patients, to try to improve the symptoms of chemo-brain in those undergoing chemotherapy and improve quality of life.

Colorectal cancer rates in the North West are 37% higher than the national average, with the lowest overall survival in England at 58.1%. Standard chemotherapy drugs such as fluorouracil, capecitabine, and oxaliplatin effectively treat tumours but can damage healthy cells, leading to side effects. One common and distressing effect is known as "chemo-brain", which involves problems with memory, attention, and thinking speed. These symptoms can reduce quality of life and increase stress.

Prehabilitation, which involves exercise and nutritional support before treatment, has demonstrated significant benefits in the surgical setting by improving cardiorespiratory fitness, physical function, and recovery. However, its role before chemotherapy is less clear. Exercise promotes both physical and brain health by increasing growth factors, improving blood flow to the brain, and supporting the formation of new brain cells and blood vessels.

This study aims to investigate whether an exercise-based prehabilitation programme can reduce the symptoms of chemo-brain, improve brain health and enhance quality of life in older adults undergoing chemotherapy for colorectal cancer. Participants aged 60-85 years with stage II or III colorectal cancer scheduled to receive chemotherapy (fluorouracil, capecitabine, or oxaliplatin) are eligible. Suitability to receive chemotherapy must be confirmed by the clinical care team via medical records.

Participants will take part in a remotely supervised exercise programme before and during chemotherapy. The programme consists of four 40-minute sessions per week, including two supervised sessions delivered via video by the lead investigator and two independent sessions supported by an exercise booklet and videos.

Each session includes a warm-up, 20 minutes of aerobic exercise at around 60% of peak fitness, strengthening exercises for upper and lower limbs using resistance bands, and a cool-down. Exercises will be adjusted based on individual ability, with progressions and regressions provided. Participants must have a family member, carer, or friend present during supervised sessions for safety. Psychological support and multivitamin supplementation will also be included.

Assessments will take place at three time points:

• Visit 1 (baseline): 3-4 weeks before chemotherapy.
• Visit 2: Within 72 hours of starting chemotherapy.
• Visit 3: 3-4 days after the final chemotherapy session. A follow-up will occur three months after chemotherapy. At each assessment, cardiorespiratory fitness (CPET), blood samples, brain activity (EEG), cognitive tests, and quality of life questionnaires will be completed.

While there is no guarantee of direct benefit, participation may improve fitness, reduce fatigue, and enhance quality of life during chemotherapy. Exercise can also support mood, manage anxiety and depression, and potentially lessen cognitive changes linked to chemotherapy. Participants will contribute to research that could help improve future cancer care.

Risks are minimal and will be closely managed. CPET carries a small risk of cardiac events or fainting, but all tests will be conducted under medical supervision with appropriate screening, warm-ups, and safety procedures in place. Exercise carries a small risk of muscle strain, but exercises will be tailored to ability.

EEG recordings are safe, though mild skin irritation may occur from the cap or cleaning solution. Blood sampling can cause minor bruising or discomfort, but it will be performed by trained professionals. Cognitive testing may occasionally cause fatigue or frustration.

All procedures will take place in hospital settings with immediate access to medical staff. Any clinical concerns identified during testing will be reported to the participant's oncology team or helpline, following consent procedures. The study will not alter or interfere with normal clinical care.

All data, including personal contact information, will be securely managed within Lancaster University's Microsoft Teams environment, ensuring full GDPR compliance. The study is run by Lancaster University in collaboration with East Lancashire Teaching Hospitals NHS Trust, Lancashire Teaching Hospital NHS Trust, and University Hospitals of Morecambe Bay NHS Trust. Recruitment and testing will take place across all participating sites.

The study is due to begin in early 2026 and will run until September 2027. This study is funded by North West Cancer Research.

Inclusion Criteria:

• Individuals with stage II or III colorectal cancer undergoing chemotherapy with fluorouracil, capecitabine, or oxaliplatin.
• Aged 60-85 years old.
• Fluent in English
• Male and female participants
• Not engaged in structured exercise training* within the six months before providing consent.

Exclusion Criteria:

• Presence of comorbidities that may significantly alter the metabolic response to exercise (e.g., diabetes mellitus).

• Current musculoskeletal injury or physical limitations that prevent completion of cardiopulmonary exercise testing (CPET).

• Any contraindication to the multivitamin supplementation (Forceval), including known hypercalcaemia, haemochromatosis, peanut or soya allergy, current use of phenytoin or tetracycline antibiotics, and clinically significant impaired renal or hepatic function.

• Evidence of pre-existing cognitive impairment, including diagnosis of dementia, other neurodegenerative disorders (e.g., Alzheimer's disease), or clinically indicated mild cognitive impairment.

• Diagnosis of atrial fibrillation and haematological malignancy.

• Participants without home internet access will be excluded due to the online delivery of the exercise programme.

• Diagnosis of profound hearing loss.

• Receiving palliative care.

• Presence of synchronous cancer.

  • Structured exercise refers to planned and organised physical activity, such as gym workouts, exercise classes or a team sport, which are designed to improve or maintain physical fitness, often with instruction, rules, and goals.