2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

ADJUVANT THERAPY FOR STAGE III COLON CANCER
Table 2. Ongoing Adjuvant Trials for Colon Cancer Testing Duration of FOLFOX or XELOX Therapy (3 versus 6 Months of Therapy)
stage II and III colorectal cancer. 39 In response to these
concerns, at least five randomized trials have opened and
are accruing patients to test the noninferiority of 3 months
compared with 6 months of a fluoropyrimidine/oxaliplatin
combination therapy (Table 2). Investigators have agreed to
pool data from all patients with stage III disease enrolled in
the trials to test for noninferiority through a preplanned
pooling project, the International Duration Evaluation of
Adjuvant Chemotherapy (IDEA) prospective pooled analysis.
Noninferiority will be declared if the two-sided 95%
confidence interval for the HR comparing 3 to 6 months of
therapy lies entirely below 1.10, which translates to an
approximately 1.5% difference in DFS.
Adjunctive Therapy Considerations
Epidemiologic and scientific research indicates that diet
and other lifestyle factors influence the risk of developing
colorectal cancer. 40 Obesity, consumption of red meat, a
Western-pattern diet, alcohol, and smoking influence one’s
risk of developing colorectal cancer; physical activity, calcium,
vitamin D, postmenopausal estrogen use, aspirin,
nonsteroidal anti-inflammatory drugs (NSAIDs), and possibly
folate decrease one’s risk. Until recently, whether these
factors influence outcomes in patients already diagnosed
with colorectal cancer was largely unknown. Data on factors
that may influence disease recurrences and mortality for
survivors of colon cancer are emerging.
Energy-Balance Factors and Colon Cancer Outcomes
Multiple prospective cohort studies have tested the influence
of physical activity before and after diagnosis and
changes in physical activity before and after diagnosis. 41-45
Haydon and colleagues reported that physical activity before
diagnosis was associated with a 51% improvement in DFS in
patients with stage II and III colorectal cancer. 46 In contrast,
physical activity before diagnosis did not influence
colorectal cancer–specific mortality in women diagnosed
with stages I to III colorectal cancer participating in the
Nurse’s Health Study, but activity after diagnosis did improve
outcomes. Compared to women engaged physical activity
less than 3 metabolic equivalent task (MET)-hours
per week (i.e., considered fairly inactive), those engaged in
at least 18 MET-hours per week (i.e., the equivalent to 1
hour of moderate walking daily at least 6 days per week)
had an adjusted HR for colorectal cancer–specific mortality
of 0.39 (95% CI, 0.18 to 0.82) and an adjusted HR for overall
TOSCA SCOT CALGB/SWOG 80,702 GERCOR HORG
Country Italy United Kingdom plus other
European sites
Principal Investigator (s) Alberto Sobrero Timothy Iveson and
Jim Paul
United States and Canada France Greece
Jeffrey Meyerhardt and
Anthony Shields
Thierry Andre and
Julien Taieb
Accrual Goal 3,500 9,500 2,500 2,000 1,000
Inclusion Criteria High risk stage II and III colon
cancer
Additional Features Previously included bevacizumab
randomization but dropped
after other bevacizumab trials
reports
Stage II and III colon and
rectal cancer
Stage III colon cancer Stage III colon
cancer
2 � 2 randomization - duration
question and celecoxib or
placebo
Ioannis Souglakos
High risk stage II
and stage III
colon cancer
mortality of 0.43 (95% CI, 0.25 to 0.74). 41 Further, women
who increased their activity after diagnosis had an HR of
0.48 (95% CI, 0.24 to 0.97) for death from colorectal cancer
and an HR of 0.51 (95% CI, 0.30 to 0.85) for death from
any cause, compared to those with no change in activity.
Similar results were seen in a cohort of male health professionals
participating in the Health Professionals Follow-up
Study. 44 These results were further supported by data from
a prospective cohort study within an adjuvant therapy trial
sponsored by the National Cancer Institute (Cancer and
Leukemia Group B [CALGB] trial 89803). 42 Among 832
patients with stage III colon cancer who survived and were
recurrence-free approximately 6 months after adjuvant
chemotherapy, physical activity after diagnosis improved
DFS by approximately 50% beyond surgery and adjuvant
chemotherapy. In addition, a recent cohort from Australia
of more than 1,800 survivors of stage I to III colorectal
cancer demonstrated that physical activity after diagnosis
improved overall mortality by approximately 25%. 45 These
data led to a multinational trial in Canada and Australia,
the Colon Health and Life-Long Exercise Change
(CHALLENGE) trial, designed to determine the effects of
a 3-year structured and supervised physical activity intervention
on disease outcomes in 962 high-risk survivors of
stage II and III colon cancer who completed adjuvant chemotherapy
within the previous 2 to 6 months. 47 The trial is
currently open to accrual.
Although the initial assumption may be that physically
active survivors of colorectal cancer have lower body mass
indexes or that exercise lowers body weight, most studies
examining obesity and colorectal cancer survival have
shown only modest associations, if any. 48 Only one study has
reported on the effect of change in weight on outcomes in
survivors of colorectal cancer. Patients enrolled in CALGB
89803 reported weight during chemotherapy and approximately
6 months after completion of chemotherapy and
change in weight or body mass index was not associated
with either DFS or OS. 49
Although various dietary factors have been associated
with the development of colorectal cancer, only one large,
prospective cohort study has tested whether diet is associated
with outcomes in survivors of colon cancer. 50 In CALGB
89803, participants completed a food frequency questionnaire
during adjuvant therapy and 6 months after the
completion of adjuvant therapy. Using these data, two major
dietary patterns were identified: prudent pattern, character-
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