Since the 1990s, a 6-month course of adjuvant chemotherapy has been the standard of care for patients with resected high-risk stage ii
colon cancer 1
. Despite recent advances in adjuvant therapy, a substantial proportion of such patients still experience disease relapse and premature death 2
. Recently published observational data suggest that physical activity (pa
) is associated with a reduced risk of disease relapse and premature death in these colon cancer survivors.
In 2006, Meyerhardt et al. 3
reported results of a prospective observational study of 832 patients with stage iii
colon cancer enrolled in a randomized adjuvant chemotherapy trial and followed for a median of 3.8 years from trial entry. In that trial, pa
was self-reported approximately 6 months after completion of chemotherapy and was quantified as weekly metabolic equivalent task (met
)–hours (for example, walking briskly is approximately 4.0 met
s). Categories of pa
were predefined in terms of these met
–hours: fewer than 3 (referent), 3–8.9, 9–17.9, 18–26.9, and more than 27. Analyses adjusted for known prognostic factors, including body mass index (bmi
), indicated that higher levels of pa
were associated with superior disease-free (dfs
), recurrence-free, and overall survival. The 3-year dfs
was 75.1% in patients who exercised for fewer than 18 met
–hours weekly as compared with 84.5% in patients who exercised for more than 18 met
–hours weekly [hazard ratio (hr
): 0.57; 95% confidence interval (ci
): 0.39 to 0.85].
In a second article, Meyerhardt et al. 4
reported results of a prospective observational study of 573 women from the Nurses’ Health Study diagnosed with stages i
colorectal cancer. Self-reported leisure-time pa
before diagnosis and 1–4 years post-diagnosis was assessed, and analyses were again adjusted for known prognostic factors, including bmi
. An inverse relationship was observed between the amount of pa
post-diagnosis and the risk of both colorectal cancer–specific and overall mortality. Specifically, as compared with women exercising for fewer than 3 met
–hours weekly, the risk of colorectal cancer–specific mortality declined in successive groups performing more exercise: the hr
was 0.92 (95% ci
: 0.50 to 1.69) in the 3–8.9 met
–hours weekly group, 0.57 (95% ci
: 0.27 to 1.20) in the 9–17.9 met
–hours weekly group, and 0.39 (95% ci
: 0.18 to 0.82) in the more than 18 met
–hours weekly group. Risk of overall mortality was similarly reduced. Furthermore, change in pa
from pre- to post-diagnosis was also predictive of outcome. Compared with women who did not change their pa
, women who increased their pa
by at least 1 predefined met
category—for example, from fewer than 3 met
–hours to 3–8.9 met
–hours—between their pre-diagnostic and post-treatment assessments experienced improved outcomes; women whose exercise levels decreased by at least 1 predefined met
category had poorer outcomes. Further analysis of these data suggested that no additional benefit accrued with an increase in pa
post-diagnosis in women who were already achieving at least 9 met
–hours weekly before diagnosis (that is, those who were roughly already meeting current public health guidelines).
Several plausible biologic mechanisms could account for an association between pa
and colon cancer outcomes, including metabolic consequences of obesity; decreased gastrointestinal transit time; decreased levels of insulin, insulin-like growth factors, and pros-taglandin ratios; lowered bile acid secretion; and altered gut flora 5
. Moreover, there is evidence that colon cancer survivors experience significant declines in pa
during adjuvant therapy 6
and that they report among the lowest pa
participation rates of any cancer survivor group 7
, suggesting that, in the current pa
levels of colon cancer survivors, there is considerable room for improvement from a public health perspective. Finally, progress has been made in the science of health behaviour change over the past decade demonstrating that pa
can, indeed, be increased substantially and maintained over extended periods of time with an appropriate behavioural support program 8–10
. Together, these observations suggest that interventions to increase pa
in colon cancer survivors may improve disease outcomes, that associated correlative biologic studies may provide insights into the mechanisms of colon cancer pathogenesis, and that sufficient understanding exists to implement an effective intervention.
Despite the highly suggestive observational findings, a randomized controlled trial (rct) is needed to establish unequivocally the causal nature of this association and to inform policies for health care delivery. The primary objective of the Colon Health and LifeLong Exercise Change (challenge) trial co.21 being undertaken by the National Cancer Institute of Canada Clinical Trials Group (ncic ctg) is to determine the effects of a 3-year structured pa intervention on dfs in survivors of high-risk stage ii or iii colon cancer who have completed adjuvant chemotherapy in the preceding 2–6 months and who are insufficiently active. Secondary objectives are to
- determine the effects of the pa intervention on important secondary endpoints including overall survival, multiple patient-reported outcomes (pros), and objective physical functioning.
- identify the determinants of long-term pa adherence in the intervention arm.
- explore the associations between selected molecular markers and study endpoint measures.
- provide an economic evaluation of the pa intervention.
We hypothesize that colon cancer survivors randomized to the pa intervention arm will experience improvements in dfs, pros, and objective physical functioning as compared with survivors allocated to general health education.