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Health Protocols

Colorectal Cancer

Novel and Emergent Modalities in Colon Cancer Prevention and Management

COX-2 Inhibitor Drugs

Aspirin. It has long been known that aspirin may offer protection from developing a variety of cancers. Recently, a large retrospective look at data over a 20-year period showed that low dose aspirin (75‒81mg) for longer than five years reduced the risk of colon cancer by 24%, and was most effective at reducing risk of right sided (proximal) colon cancer, a staggering 70%!4 Importantly, not just risk of being diagnosed, but also the risk dying from colon cancer was reduced by up to 40% in those that took aspirin (any dose) for over five years.17

Aspirin’s anticancer properties stem in part from its capacity to inhibit the action of cyclooxygenase-2 (COX-2), an enzyme that plays a central role in onset and progression of most cancers, and is overactive in 50% of adenomas and 80% of colorectal cancers.77-79 Aspirin also beneficially modulates activity of the protein complex nuclear factor-kappa B (NF-kB), the so-called “master switch” that stimulates the growth of a variety of cancers, including colorectal cancers.80

Celecoxib. Celecoxib is a non-steroidal anti-inflammatory drug (NSAID) that inhibits COX-2. In one study, 1,561 individuals with a history of adenomas were recruited to take either celecoxib (400 mg/day) or placebo. Follow-up colonoscopies at three years found that the risk of developing adenomas was halved in the celecoxib group.81 One study suggested a synergistic effect when celecoxib is taken with fish oil.82 However, while celecoxib can lessen adenoma formation, it is also well documented to raise the risk of cardiovascular events,83,84 leaving a risk/benefit equation that should be seriously considered.

Note: additional information about inhibiting the COX-2 enzyme can be found in step four of the “Cancer Treatment: The Critical Factors” protocol.


Metformin is an oral antidiabetic drug that works by suppressing the production of glucose in the liver and boosting insulin sensitivity in peripheral tissues. Metformin is currently considered the treatment of choice for type 2 diabetes.

As with other malignancies, colorectal cancer risk is increased in diabetics, and there is a growing body of evidence that advanced glycation end products (AGEs), which are a consequence of elevated blood glucose, and insulin-receptor signaling are involved in the initiation and propagation of these common tumors.85,86

Moreover, colorectal cancers are among those malignancies most closely associated with obesity. Obese individuals are deficient in the protective hormone adiponectin, which activates tumor-suppressing AMPK. Metformin, by independently activating AMPK, may circumvent this deficiency and help to reduce its impact on colorectal cancer risk.87 Naturally, these findings have piqued interest in investigating the potential role of metformin against colorectal cancer.

In 2011, researchers conducted a comprehensive review of observational data on the use of metformin and the risk of colorectal cancer in diabetic patients.88 This review encompassed five studies including nearly 110,000 subjects. Compared to all other antidiabetic treatments, the use of metformin was associated with a 37% lower risk of colorectal cancer.

While this review provides compelling data in support of the protective role of metformin against colorectal cancer, it should be noted that the trials included were observational in nature; the protective effects of metformin must still be substantiated in clinical intervention trials.

Nonetheless, Life Extension suggests colorectal cancer patients, especially those who are overweight or have a fasting glucose level of greater than 85 mg/dL, ask their healthcare provider if metformin would be a positive addition to their regimen.


Cimetidine (Tagamet) reduces the production of stomach acid by binding with H2 receptors on the acid-secreting cells of the stomach lining. These receptors normally bind with histamine to produce stomach acid, which helps to break down food. By competing with histamine to bind with H2 receptors, cimetidine reduces the stomach’s production of acid. This mechanism of action accounts for cimetidine’s use in managing gastroesophageal reflux disease (GERD), a condition marked by an excess of stomach acid. Before stronger antiemetic drugs became available, cimetidine was prescribed to treat nausea associated with chemotherapy. As far back as 1988, scientists observed that colon cancer patients who had been treated with cimetidine had a notably better response to cancer therapy than those who did not receive cimetidine.89

Cimetidine functions via several different pathways to inhibit growth of tumors. It inhibits proliferation of cells, blocks new blood vessel growth, and interferes with cell to cell adhesion, a necessary process in the spread of cancer.90 It also has positive effects on immune function.

In a 1994 study, just seven days of cimetidine treatment (400 mg twice daily for five days preoperative and intravenously for two days post-operative) in colorectal cancer patients decreased their three-year mortality rate from 41% to 7%. In addition, tumors in the cimetidine-treated patients had a notably higher rate of infiltration by lymphocytes, a type of white blood cell.91 These tumor-infiltrating lymphocytes, part of the body’s immune response to the tumor, serve as a good prognostic indicator.

Since cimetidine is a histamine receptor antagonist—that is, an agent that binds with a cell receptor without eliciting a biological response—it may help circumvent immunosuppression caused by increased histamine levels in a tumor’s microenvironment.92 While histamine appears to stimulate the growth and proliferation of certain types of cancer cells, inhibiting histamine’s action may be only one mechanism by which cimetidine fights cancer.

Cimetidine inhibits cancer cell adhesion by blocking the expression of an adhesive molecule—called E-selectin—on the surface of endothelial cells that line blood vessels.93 Cancers cells latch onto E-selectin in order to adhere to the lining of blood vessels.94 By preventing the expression of E-selectin on endothelial cell surfaces, cimetidine significantly limits the ability of cancer cell adherence to the blood vessel walls.

Administering cimetidine may enable the immune system to mount a more effective response, possibly minimizing the risk of growth and spread from surgical resection of the tumor. Recent studies suggest that cimetidine enhances local tumor response through the production of Interleukin-18 (IL-18) by immune cells (monocytes).95 IL-18 blocks new blood vessel growth and encourages apoptosis of cancer cells.

A report in the British Journal of Cancer examined findings of a collaborative colon cancer study conducted by 15 institutions in Japan. First, all participants had surgery to remove the primary colorectal tumor, followed by intravenous chemotherapy treatment. They were then divided into two groups: one group received 800 mg of oral cimetidine and 200 mg of fluorouracil (a cancer-fighting medication) daily for one year, while a control group received fluorouracil only. The patients were followed for 10 years. Cimetidine greatly improved the 10-year survival rate: 85% of the cimetidine-treated patients survived 10 years, compared to only 50% of the control group.96 Cimetidine produced the greatest survival-enhancing benefits in those whose cancer cells showed markers associated with the tendency to metastasize.

Several other studies have corroborated cimetidine’s benefits in colorectal cancer. For instance, in a Japanese study in 2006, colorectal cancer patients who received cimetidine following surgical removal of recurrent cancer had an improved prognosis compared to those treated with surgery alone.97

Vaccines and Immunotherapies

An enlightened medical approach to cancer treatment involves the use of cancer vaccines. The concept is the same as using vaccines for infectious diseases, except that tumor vaccines target cancer cells instead of a virus. Another distinguishing feature of tumor vaccines is that while viral vaccines are created from a generic virus, tumor vaccines can be autologous, that is, they can be produced using a person’s own cancer cells that have been removed during surgery. This is a critical distinction since there can be considerable genetic differences between cancers. This highly individualized cancer vaccine greatly amplifies the ability of the immune system to identify and target any residual cancer cells present in the body. Cancer vaccines provide the immune system with the specific identifying markers of the cancer that can then be used to mount a successful attack against metastatic cancer cells.

Autologous cancer vaccines have been studied extensively, with the most encouraging results noted in randomized, controlled clinical trials including more than 1,300 colorectal cancer patients in which tumor vaccines were given after surgery. These trials reported reduced recurrence rates and improved survival.98 Unlike chemotherapy, which can cause severe side effects and toxicity, cancer vaccines offer the hope of a “gentler” type of therapy with improved long-term safety.99

In a landmark study reported in 2003, 567 individuals with colon cancer were randomized to receive surgery alone, or surgery combined with vaccines derived from their own cancer cells. The median survival for the cancer vaccine group was over seven years, compared to the median survival of 4.5 years for the group receiving surgery alone. The five-year survival was 66.5% in the cancer vaccine group, which dwarfed the 45.6% five-year survival for the group receiving surgery alone.100 This glaring difference in five-year survival clearly displays the power of individually-tailored cancer vaccines to greatly focus a person’s own immunity to target and attack residual metastatic cancer cells.

Monoclonal antibody therapies currently employed in colorectal cancer therapy include bevacizumab, which targets VEGF, and panitumumab and cetuximab, which target EGFR.

For a detailed discussion of cancer vaccines, please review the “Cancer Immunotherapy” protocol.

Personalizing Your Cancer Treatment Regimen

All cancers, including colon cancer, can have unique genetic characteristics from person to person. Gene expression profiles can highlight minute differences in the character of a cancer, and help identify which anticancer drugs will be most effective.

In one study, a 50-gene array conducted on resected colon cancers (stage I or II patients) determined that those with more “aggressive” patterns may be ideal candidates for interventions with specific preventative agents such as COX-2 inhibiting agents.101 Such testing may be able to determine with great precision which natural or prescriptive agent to choose based on the molecular characteristics of the cancer. Specifically, tests for KRAS mutational status, EGFR expression, microsatellite instability, and other relevant tests are available currently.

Cancers have traditionally been treated as follows: if one therapy proves ineffective, then try another until a successful therapy is found or all options are exhausted. Evaluating the molecular biology of the tumor cell population helps to eliminate the need for this trial-and-error method by providing individualized information to help determine the optimal therapy before initiating treatment. This can save the patient time and money and most importantly, it may provide a better opportunity for "first strike" eradication.

Life Extension recognizes the value that advanced cancer testing delivers to cancer patients and suggests that every cancer patient test their cancers as extensively as possible. For more information on testing the unique biological characteristics of your cancer, refer to steps one and two of the “Cancer Treatment: The Critical Factors” protocol.