2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

ized by high fruit, vegetable, poultry, and fish intakes, and
Western pattern, characterized by high meat, fat, refined
grains, and dessert intakes. All patients were assigned a
relative value along the spectrum of both dietary patterns
and the two patterns were not correlated with each other.
Compared with patients in the lowest quintile of the
Western-pattern diet, those in the highest quintile experienced
an adjusted HR for DFS of 3.25 (95% CI, 2.04 to 5.19;
p for trend � 0.0001). In contrast, the prudent-pattern diet
was not significantly associated with cancer recurrence or
mortality. Studies on the components of the Westernpattern
diet that influenced these findings are underway.
NSAIDs, Vitamin D, and Colon Cancer Outcomes
Outside of energy-balance factors, research is emerging on
the effects of aspirin, NSAIDs, and vitamin D. Prospective
cohort studies have demonstrated that aspirin and NSAIDs
reduce the risk of developing colorectal cancer, and several
randomized trials have shown that these agents reduce the
number of subsequent polyps in patients with a history of
adenomatous polyps. 51-54 Initial studies have also shown a
beneficial association of these agents for survivors of colorectal
cancer. 55 In the CALGB 89803 cohort of patients with
stage III colon cancer, regular use of aspirin (defined as
consistent use both while receiving adjuvant therapy and for
6 months after the completion of adjuvant therapy) had a
significant 54% improvement in DFS compared with patients
that did not regularly use aspirin (p � 0.001). 55
Similarly, for patients with stages I to III colorectal cancer
from both the Nurse’s Health Study and Health Professional
Follow-up Study, regular aspirin users had a more modest
but still significant improvement in colorectal cancer mortality
compared to nonusers (HR � 0.72; 95% CI, 0.54 to
0.97, p � 0.03). 56
The Vioxx in Colorectal Cancer Therapy: Definition of
Optimal Regime (VICTOR) trial was a randomized controlled
trial in the United Kingdom evaluating the role of
rofecoxib, a cyclooxygenase 2 inhibitor, for patients with
stage II and III colon cancer who completed adjuvant therapy.
57 The trial activated in April 2002 but was terminated
in September 2004 after the withdrawal of rofecoxib from
the market. Before study closure, 2,434 patients were randomly
assigned to placebo, 2 years of rofecoxib, or 5 years of
rofecoxib, with a median duration of time on trial of 7.4
months. The HR for DFS with a median follow-up of 3 years
was 0.90 (95% CI, 0.77 to 1.06), favoring rofecoxib among
patients with stage II and III disease. However the early
closure of the trial and the limited time patients received the
study medication in relationship to the intent of the trial
limit conclusions from this trial. Given the observational
Authors’ Disclosures of Potential Conflicts of Interest
Author
Employment or
Leadership
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Consultant or
Advisory Role
data and the potential benefit seen in VICTOR, the CALGB
and Southwestern Oncology Group (SWOG) have developed
a trial (CALGB/SWOG 80702, Table 2) that tests the duration
of FOLFOX therapy, with a second randomization of
celecoxib compared with placebo initiated concurrent with
the start of FOLFOX and continuing for 3 years. The trial
will test for superiority in DFS of celecoxib compared with
placebo.
Increasing evidence suggests an association between vitamin
D and development of colorectal cancer. A metaanalysis
of five epidemiologic studies found a 51% decrease
in the risk of colorectal cancer associated with plasma
25(OH)D levels in the highest quintile compared to those in
the lowest quintile (p � 0.0001). 58 Although studies on
vitamin D in patients with colon cancer are limited, two
recent studies by Ng and colleagues using the Nurse’s
Health Study and the Health Professional Follow-up Study
cohorts suggest that either higher levels of serum vitamin D
before diagnosis or greater predictive vitamin D serum
levels are associated with improved colorectal cancer–specific
mortality, overall mortality, or both. 59,60
Conclusion
Adjuvant chemotherapy has taken an important place in
the treatment of patients with stage III colon cancer. The
5-year survival of patients with stage III colon cancer has
increased from less than 50% with surgery alone (before
1990) to more than 70% with surgery followed by adjuvant
fluoropyrimidines combined with oxaliplatin (since 2003).
However, despite this progress, multiple disappointments
have emerged including the realization that three of the four
agent classes approved for metastatic colorectal cancer since
1995 have failed to improve the chance of cure for patients
with stages II and III colorectal cancer. We must learn from
the experiences of these trials to avoid future expensive
failures, and must also begin to consider that not all colon
cancers are the same. The future, as is the case for most
areas of cancer, must involve rational trial designs based
on well-characterized and clinically validated biology. The
study of agents with marginal survival benefit in unselected
populations is discouraged based on the experiences outlined
above. Although most of the current trials are not
adding new agents to FOLFOX (with the exception of the
CALGB/SWOG 80702 trial), the focus on the potential for
less therapy and presumed less long-term neuropathy is
important. Finally, beyond standard chemotherapies, continued
research on other adjunctive therapies is critical to
further understand the role of energy balance and other host
factors in colon cancer survival.
Stock
Ownership Honoraria
Research
Funding
Thierry André Roche; Sanofi Baxter
International;
Roche; Yacult
Bert H. O’Neil Amgen;
Bayer/Onyx
Amgen
Jeffrey A. Meyerhardt Bayer AstraZeneca;
Bristol-Myers
Squibb
228
ANDRÉ, O’NEIL, AND MEYERHARDT
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