Primary cancer prevention: prophylactic measures to intercept
Chemoprevention: pharmacologic blocking of intrinsic oncogene-
or carcinogen-induced cell proliferation and transformation.
Secondary/tertiary prevention: screening, surveillance.
- • General population at risk.
- • High-risk population (eg, status post polypectomy
or cancer resection).
Positive Effect Documented
Reduced endogenous prostaglandin: COX-2 not elevated in normal
colon epithelium, overexpressed in 40–50% of colorectal
adenomas, 90% of colorectal cancers.
- • Long-term use of ASA: reduction in incidence
of colorectal polyps.
- • Sulindac: delay of polyp formation and regression
of large bowel polyps in FAP.
- • Selective COX-2 inhibitors (celecoxib, rofecoxib):
same benefits plus presumed less ulcerogenic, but increased cardiac
Decreased incidence of recurrent colorectal adenomata.
Mechanism: intraluminal binding of bile and fatty acids, direct
antiproliferative effect in colonic mucosa.
Decreased incidence of colorectal cancer.
Mechanism: through calcium effect, direct antiproliferative
effect of Vitamin D?
Controversial or Awaiting Further Confirmation
- • Fiber: benefit is supported by epidemiologic
association and “gut feeling” but has not been
confirmed by prospective trials.
- • Folate.
- • Ursodeoxycholic acid.
- • Hormone replacement therapy → reduction
in incidence of colorectal cancer and cancer-specific mortality.
- • Selenium.
- • Vitamins C and E.
- • β-Carotenes.
Chemotherapy has evolved as a cornerstone in the treatment
of various cancers. There is a large number of known chemotherapy
agents overall with a wide range of mechanisms of action, but a limited
number of drugs are commonly used in the realm of colorectal surgery
patients. Selection of specific drugs, protocol, routes of administration,
timing, and duration depend on several patient- and tumor-related
- • Antimetabolites: 5-fluorouracil (+ leucovorin),
- • Platin-based alkylating agents: oxaliplatin, carboplatin,
- • Topoisomerase inhibitors: irinotecan.
- • Targeted immunotherapy (monoclonal antibodies):
bevacizumab, cetuximab, panitumumab.
- • Cytotoxic/antitumor antibiotics: mitomycin
- • Tyrosine kinase inhibitors: imatinib, sunitinib.
Antimetabolite (pyrimidine analogue).
Intracellular conversion to active metabolites → combined
cytotoxic effect from inhibition of thymidylate synthase ...