# Exercise as it relates to Disease/Tired of cancer; exercise as a means of reducing fatigue in chemotherapy patients

The following is an analysis of the research article "Effects of an Exercise Program in Colon Cancer Patients undergoing Chemotherapy" by van Vulpen et al. (2016)

### What is the background to this research?

Colon cancer (CC) is the third most common cancer, behind lung and breast cancers, with an estimated 1.4 million new cases diagnosed worldwide in 2012. A common symptom shared by all cancers, including CC, is cancer related fatigue (CRF). Prevalence of CRF is known to vary greatly (10-90%) between different types of cancer, stages of the cancer and stages of the treatment. However, it has been seen that levels of fatigue significantly increase in patients with CC who undergo chemotherapy.
CRF can be debilitating to suffers physically, cognitively, socially and financially. A study of patients who had undergone chemotherapy and experienced fatigue showed that of the 379 participants, 91% said that fatigue prevented a normal life and 88% said it impacted their daily routine. At least 30% reported that they found common activities such as socialising with friends, grocery shopping and going out to a restaurant difficult. Of 177 participants who were employed, 75% had changed their employment status. Other research has shown that high levels of fatigue in cancer patients correlated strongly with longer sit to stand times and lower grip strengths. Patients with CRF commonly reported symptoms linked with psychological impairment such as depression, anxiety and lack of motivation.
Previous studies have shown that prescribed exercise programs may be beneficial in reducing CRF in cancer patients. However, there is little evidence to suggest that CRF is reduced with a prescribed exercise program in CC patients also undergoing chemotherapy.

### Where is the research from?

This study was conducted across 7 hospitals in the Netherlands. The results of this study may translate over to an Australian population of European descent. However, findings may not necessarily be comparable with, for example, an Indigenous Australian population.
The study was published in Medicine and Science in Sports and Exercise, a reputable monthly peer-reviewed journal of the Americal College of Sport and Medicine (ACSM).
The lead author of the study, JK van Vulpen, has recently published a meta-analysis in the British Journal of Sports Medicine and a case-control study the International Journal of Epidemiology. Their research generally focuses on the effects of exercise in cancer patients.

### What kind of research was this?

This study was a randomised controlled trial (RCT). It was part of a two-arm study, the Physical Activity during Cancer Treatment (PACT) study, in which patients with breast cancer or colon cancer were included. Only results for colon cancer patients are presented in this study.
RCTs are considered good sources of information, with a high level of evidence.

### What did the research involve?

84 CC patients were identified as meeting the criteria to participate in the study by their medical specialist or oncology nurse. Of these, 33 participants signed informed consent and were included in the study. These participants were randomised on a 1:1 ratio into the intervention group or into a usual care group.
The intervention group participated in an 18wk exercise program. The program consisted of 2x1hr sessions per week with a 10min warm up, 40min aerobic and strength training and a 10min cool down supervised by a physiotherapist. The exercise program was catered to the participant based on preference and intensity was determined by baseline physical fitness. Participants in this group were also instructed to, in addition to the supervised exercise program, be physically active on 3 other days for at least 30min in accordance with Dutch physical activity guidelines.
Patients in the usual care group served as the control group and received no supervised exercise program and were instructed to maintain their usual levels of physical activity.
| Outcome Measure | Measurment |
| Fatigue | MFI and FQL questionnaires |
| QoL, anxiety and depression | EORTC QLQ-C30 questionnaire |
| Physical fitness | peak VO$_2$, HR and power output, O$_2$ consumption and power output at ventilatory threshold |
| Anthropometry | weight and height |
| Chemotherapy completion rate | fraction of completed dose vs planned dose |
| Adherence and PA levels | exercise log, SQUASH questionnaire |

### What were the basic results?

Participants in the intervention group reported significantly less physical fatigue at 18 weeks. A reduction was also seen at 36 weeks however this difference was not statistically significant. General fatigue was lower in the intervention group at 36 weeks. Physical functioning was significantly higher for the intervention group at 36 weeks. No significant differences were seen between groups for levels of anxiety and/or depression.
There were no significant differences seen between groups as a whole regarding measures of physical fitness or weight. However, when the authors only looked data for either males or females alone there were statistically significant differences. Males in the intervention group experienced significant reductions in peak power output and peak VO¬2 kg-1 at 36 weeks, while females in the intervention group experienced significant increases in all fitness measures except peak HR at 36 weeks.
No significant differences were seen for chemotherapy completion rates between groups.
No adverse exercise related events were observed during the study in either group.

### What conclusions can we take from this research?

The authors of the study warn that caution should be taken when interpreting the above results due to the studies low participation rate (33 participants). Bearing this in mind the results from this study indicate that a supervised exercise program can be safe for patients with colon cancer while not interfering with their chemotherapy treatment. It also shows that exercise may be effective in reducing general and physical fatigue felt by these patients. The results of similar studies are conflicting, with a meta-analysis finding that exercise does not reduce CRF in chemotherapy patients.
It is interesting to note that participants in the study self-reported that they performed moderate intensity (or equivalent of high intensity) exercise ranging from 240-990 min/week before commencing the intervention. While the over exaggeration of self-reported physical activity levels is well documented these are very high levels of physical activity. Therefore, the small sample within this study does not represent the average Australian, only 55% of Australian adults perform atleast 150 min/week of moderate PA. However, one could postulate that a population that is not currently meeting physical activity guidelines might see even greater reductions in cancer related fatigue when given a supervised exercise program due to an increase from baseline physical activity or reduction in sedentary behaviour.
Studies with not only greater sample size but also baseline physical activity levels reflecting that of the broader population are needed to determine the true relationship between exercise and fatigue in CC patients undergoing chemotherapy.

### Practical advice

Results of this and other similar studies can aid oncology wards in developing structured exercise programs for patients diagnosed with colon cancer to help possibly improve their quality of life by reducing the amount of fatigue they feel during their chemotherapy treatment.
It is important that individuals planning on increasing their weekly physical activity levels consult their health professional beforehand.

### Further information/resources

Bowel Cancer Australia Helpline: 1800 555 494 10am-4pm Monday to Friday, or email bowelcanceraustralia.org/nurse
Bowel Cancer Australia Factsheet
A meta-analysis showing there is a strong association of physical inactivity with CC diagnosis (relative risk of 1.30).
A 4 year follow up of the PACT study showed that the intervention group had lower levels of fatigue and reported higher levels of physical activity.

### References

* ↑ Van Vulpen JK, Velthuis MJ, Steins Bisschop CN, Travier N, Van Den Buijs BJW, Backx FJG, Los M, Erdkamp FLG, Bloemendal HJ, Koopman M, De Roos MAJ, Verhaar MJ, Bokkel-Huinink DT, Van Der Wall E, Peeters PHM and May AM. 2016. Effects of an Exercise Program in Colon Cancer Patients undergoing Chemotherapy. Medicine and Science in Sports and Exercise. 48(5): 767-775 free access here
* ↑ Colorectal Cancer Statistics 2012. World Cancer Research Fund International. https://www.wcrf.org/int/cancer-facts-figures/data-specific-cancers/colorectal-cancer-statistics
* ↑ Lawrence DP, Kupelnick B, Miller K, Devine D and Lau J. 2004. Evidence report on the occurrence, assessment and treatment of fatigue in cancer patients. Journal of the National Cancer Institiute. Monographs. (32):40-50
* ↑ Vardy JL, Dhillon HM, Pond GR, Renton C, Dodd A, Zhang H, Clarke SJ and Tannock IF. 2016. Fatigue in people with localized colorectal cancer who do and do not receive chemotherapy: a longitudinal prospective study. Annals of Oncology. 27(9):1761-1767
* ↑ Curt GA, Breitbart W, Cella D, Groopman JE, Horning SJ, Itri LM, Johnson DH, Miaskowski C, Scherr SL, Portenoy RK and Vogelzang NJ. 2000. Impact of cancer-related fatigue on the lives of patients: new findings from the fatigue coalition. The Oncologist. 5(5):353-360
* ↑ Brown DJ, McMillan DC and Milroy R. 2005. The correlation between fatigue, physical function, the systemic inflammatory response, and psychological distress in patients with advanced lung cancer. Cancer. 103(2):377-382
* ↑ Stone P, Richards M, A'Hern R and Hardy J. 2000. A study to investigate the prevalence, severity and correlates of fatigue among patients with cancer in comparison with a control group of volunteers without cancer. Annals of Oncology. 11(5):561-567
* ↑ Cramp F and Daniel J. 2008. Exercise for the management of cancer-related fatigue in adults. Cochrane Database of Systematic Reviews. 16(2):CD006145
* ↑ Sackett DL, Rosenberg WM, Gray JA, Haynes RB and Richardson WS. 1996. Evidence based medicine: what it is and what it isn’t. British Medical Journal. 312(7023):71-72
* ↑ Cramer H, Lauche R, Klose P, Dobos G and Langhorst J. 2014. A systematic review and meta-analysis of exercise interventions for colorectal cancer patients. European Journal of Cancer Care. 23(1):3-14
* ↑ Dyrstad SM, Hansen BH, Holme IM and Anderssen SA. 2014. Comparison of self reported versus accelerometer measured physical activity. Medicine and Science in Sports and Exercise. 46(1):99-106
* ↑ Australian Bureau of Statistics (ABS). 2013. Australian Health Survey: Physical Activity. 2011-12. ABS Catalogue number 4364.0.55.004
* ↑ Cong YJ, Gan Y, Sun HL, Deng J, Cao SY, Xu X and Lu ZX. 2014. Association of sedentary behaviour with colon and rectal cancer: a meta-analysis of observational studies. British Journal of Cancer. 110:817-826
* ↑ Witlox L, Hiensch AE, Velthuis MJ, Steins Bisschop CN, Los M, Erdkamp FLG, Bloemendal HJ, Verhaar M, Huinink D, van der Wall E, Peeters PH and May AM. 2018. Four year effects of exercise on fatigue and physical activity in patients with cancer. BMC Medicine. 16:86