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Principle

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Primary cancer prevention: prophylactic measures to intercept tumor development.

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Chemoprevention: pharmacologic blocking of intrinsic oncogene- or carcinogen-induced cell proliferation and transformation.

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Alternatives

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Secondary/tertiary prevention: screening, surveillance.

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Indications

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  • • General population at risk.
  • • High-risk population (eg, status post polypectomy or cancer resection).

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Positive Effect Documented

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COX Inhibitors

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Reduced endogenous prostaglandin: COX-2 not elevated in normal colon epithelium, overexpressed in 40–50% of colorectal adenomas, 90% of colorectal cancers.

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  • • 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 risk.

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Calcium (3 g/Day)

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Decreased incidence of recurrent colorectal adenomata.

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Mechanism: intraluminal binding of bile and fatty acids, direct antiproliferative effect in colonic mucosa.

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Vitamin D

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Decreased incidence of colorectal cancer.

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Mechanism: through calcium effect, direct antiproliferative effect of Vitamin D?

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Positive Effect Controversial or Awaiting Further Confirmation

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  • • 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.

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Positive Effect Not Documented

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  • • Vitamins C and E.
  • • β-Carotenes.

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Cross-Reference

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Principle

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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 factors.

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Mechanism of Action Categories

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  • • Antimetabolites: 5-fluorouracil (+ leucovorin), capecitabine, gemcitabine.
  • • Platin-based alkylating agents: oxaliplatin, carboplatin, cisplatin.
  • • Topoisomerase inhibitors: irinotecan.
  • • Targeted immunotherapy (monoclonal antibodies): bevacizumab, cetuximab, panitumumab.
  • • Cytotoxic/antitumor antibiotics: mitomycin C.
  • • Tyrosine kinase inhibitors: imatinib, sunitinib.

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Specific Drugs

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5-Fluorouracil (+ Leucovorin)

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Antimetabolite (pyrimidine analogue).

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Mechanism of Action
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Intracellular conversion to active metabolites → combined cytotoxic effect from inhibition of thymidylate synthase ...

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