Changes in Aerobic Capacity and Body Composition in Colon Cancer Patients Receiving Chemotherapy

Background Information: Recent evidence has suggested that the physical activity levels and body composition of colorectal cancer survivors can impact the disease-free and overall survival following diagnosis, with those individuals who are more overweight or obese and less active at greater risk of a recurrence of or dying from colorectal cancer (Meyerhardt et al, 2006a,b; Digman et al, 2006). Chemotherapy treatments have been shown to improve survival in a number of cancer populations, but unfortunately they have also been shown to negatively impact numerous physiological and psychological variables, including reduced exercise capacity, self-reported physical functioning and activity levels, and negative changes in body composition (Schmitz et al, 2005). This suggests that chemotherapy treatments may negatively impact variables that have been associated with survival in individuals diagnosed with colorectal cancer. However, this research has been conducted in cancer populations other than colorectal cancer patients, hence the specific impact of the chemotherapy treatments for colorectal cancer on these outcomes is not known.

Objectives: The primary objective of the study is to determine the effects of chemotherapy treatments on the aerobic capacity and body composition of colon cancer patients. Secondary objectives are to determine the effects of chemotherapy treatments on quality of life, fatigue, performance status, self-reported and objectively measured physical functioning, exercise behaviour, oxygen uptake kinetics, muscular strength, and anthropometric variables.

Study Design: The study parameters assessed will include descriptive information on demographic, lifestyle and medical variables; a graded exercise test with metabolic measurement to determine peak oxygen consumption (VO2peak); air-displacement plethysmography (BOD POD) testing and anthropometric measurements (waist & hip circumferences, waist-to-hip ratio, body mass index) to assess body composition; a questionnaire to determine cancer-specific quality of life and fatigue (Functional Assessment of Cancer Treatment - Colorectal and Fatigue); performance status assessment (Eastern Cooperative Oncology Group performance status); self-reported (Medical Outcomes Study Short Form-36 Physical Function Scale) and objectively measured (Physical Functional Performance-10 and Senior's Fitness Tests) physical functioning; self-reported exercise behavior (Godin Leisure Time Exercise Questionnaire); submaximal exercise test with metabolic measurement to determine oxygen uptake kinetics; an 8-repetition maximum test to assess upper (bench press) and lower (leg press) body muscular strength; and a fasted blood sample to be used for future biomarkers assays. All of these assessments will be completed at baseline prior to the subject's first chemotherapy infusion, and 1 and 6 months after the completion of all chemotherapy infusions.

The following calculation was used to estimate the required sample size based on the primary outcome of aerobic capacity (Peak Oxygen Consumption; VO2peak): n = 2 + C (s/d)2 (Snedecor et al, 1989), where C is a constant equal to 7.85 for a power of 0.80 and alpha of 0.05, s is the standard deviation of 6.0 ml/kg/min, and d is a 3.5 ml/kg/min difference between groups. Therefore, a sample size of 25 subjects is required to detect a 1 Metabolic Equivalent (MET) or 3.5 ml/kg/min reduction in VO2peak in colorectal cancer survivors following the completion of chemotherapy treatment, with a standard deviation (SD) in oxygen consumption of 6.0 ml/kg/min, a power of 0.80, and an alpha set at p<0.05 (two-tailed). Each 1 MET change in exercise capacity has been positively associated with a 12% difference in overall survival in the general population (Myers et al, 2002). A sample of 30 subjects will be recruited to account for any subjects lost to follow-up. To compare the effects of chemotherapy treatment on the study assessments to colon cancer surgery alone, 10 subjects will be recruited to complete all of the study assessments at the same 3 time points to allow for a "surgery only" comparison group.

Inclusion/Exclusion Criteria: Inclusion criteria will include: 1)histologically confirmed colon cancer (Stage III and those Stage II patients deemed high-risk 2) approval of the treating oncologist 3) they will receive chemotherapy 4) able to understand and provide written informed consent in English 5) 18+ years of age 6) no uncontrolled co-morbidities (including hypertension, cardiac illness, psychiatric condition, etc.) negative ECG as assessed during maximal graded exercise test *Ten patients meeting all eligibility requirements except for criteria 3 will be recruited to the study to serve as "surgery only" controls.