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Natural Medicines in the Clinical Management of Colon
Cancer

Colon Cancer Treatment |

Colon Cancer Prevention |
Polyp Reduction
Bile Acids |
Controlling Gene Mutations that Lead to Cancer |
Repairing Oxidative Damage that Leads to Cancer
The Bottom Line |
References
 

There
are few conditions where diet and nutrients are thought to play a more prominent
role than in colon cancer. It makes sense. What we eat has a direct impact on our
gastrointestinal tract. As a result of this logical
connection, intense research has been  
focused on the impact of diet on colon cancer risks to determine which factors increase
risk and which factors decrease risk.
 

Researchers have sketched out the major steps that lead to colon cancer.
They describe
a "multiple hit theory," in which a series of gene mutations first cause normal epithelial The
editors of this
activity and its publisher,
cells in the colon to proliferate, then to form a benign adenoma (polyp). As the genetic
Therapeutic Research

"hits" continue, the polyp converts to a malignant tumor. These mutations might be due

Center, have no relevant
to environmental exposures (e.g., diet) and/or heredity. These mutations turn on some financial interests
genes that promote the development of tumors, while turning off other genes that related to the products
suppress tumor
growth.2263 Therapies that interrupt this process, including
certain foods or services covered by
and nutrients, are of great interest to researchers in this area. this CME/CE activity.

Despite decades of research, there are very few conclusive answers about
the best way
to reduce risks. The good news is that lots of attention is now being focused on
PREVENTION. (Remember Katie Couric from the Today Show undergoing a live
colonoscopy?) Prevention is key when it comes to colon cancer.

In fact, home screening tests for colon cancer are now available. They work about as
well as the old guaiac tests. To learn more about these tests, see new take-home
screening tests for colon cancer, an article from Pharmacist's Letter/Prescriber's Letter.

For patients who develop colon cancer, the prognosis depends on how far the cancer
has progressed before being detected and treated. For about 56,000 people in the US
each year, treatment is not curative. Colon cancer is in second place among cancer
killers. Only lung cancer takes more lives.12325

Causes of Cancer Related Death

1. Lung Cancer 157,300
2. Colorectal Cancer 51,370
3. Breast Cancer 39,840
4. Prostate Cancer 32,050
Source: American Cancer Society 2010

Commonly Used Conventional and Natural Medicines for Colon Cancer*

Treatment

Chemotherapy
Conventional Medicines
5-fluorouracil +/- folinic acid (Leucovorin)
Bevacizumab (Avastin)
Capecitabine (Xeloda)
Cetuximab (Erbitux)
Irinotecan (Camptosar)
Oxaliplatin (Eloxatin)  
Panitumumab (Vectibix)
Ralitrexed (Tomudex)
Natural Medicines
Hydrazine sulfate
Shark cartilage (Squalus acanthias)

Prevention

Anti-inflammatory Agents
Conventional Medicines
Aspirin

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Natural Medicines - Clinical Management Series: Natural Medicines

Celecoxib
Ibuprofen
Naproxen
Rofecoxib
Natural Medicines
Turmeric (Curcuma longa)
Antioxidants
Natural Medicines
Lutein
Lycopene
Vitamin C
Vitamin E
Bile Acid Reducers
Conventional Medicines
Estrogen
Ursodiol
Natural Medicines
Calcium/Vitamin D
Olive oil (Olea europaea)
Carcinogen Inhibitors
Natural Medicines
Indole-3-carbinol
Sulforaphane
Fiber
Natural Medicines
Barley (Hordeum vulgare)
Blond psyllium (Plantago ovata)
Oat bran (Avena sativa)
Oats (Avena sativa)
Wheat bran (Triticum aestivum)
Miscellaneous
Natural Medicines
Folic acid

*Note: Many natural products are tried for colon cancer, but very few have reliable evidence
that they work. Inclusion in this list does NOT imply that these products are
effective for colon
cancer.

Colon Cancer Treatment  

Treatment
options for existing colon cancer are limited. Surgery, combined with

adjunctive chemotherapy, is the standard treatment. Specific treatment approach
depends in part on the stage of the cancer.

Stages of Colon Cancer

Stage 0: Very early cancer on the innermost layer (more accurately
considered a precursor to cancer)
Stage I: Tumor in the inner layers of the colon
Stage II: Tumor that has spread through the muscle wall of the colon
Stage III: Tumor that has spread to the lymph nodes
Stage IV: Tumor that has spread to distant organs

For stages 0 and I, surgery is performed to remove the affected portion of the colon. For
stages II, III, and IV, surgery plus chemotherapy is often used; however, the use of
chemotherapy in stage II is quite controversial.

5-fluorouracil is the gold standard chemotherapy agent. Other agents include
bevacizumab (Avastin), cetuximab (Erbitux), capecitabine (Xeloda), irinotecan
(Camptosar), and oxaliplatin (Eloxatin).

Some patients turn to natural products with purported anticancer properties to help treat
a variety of cancers. What products do you see your patients taking? Consider starting a
   
Question #1
discussion on Colleagues Interact.
Which of the following is

One of the most common of these "anticancer" natural products is shark cartilage. TRUE about shark
People used to say that "sharks don't get cancer" therefore, it makes sense that they cartilage?
must have some special protective mechanism, right? It turns out to be wrong. Sharks a. It seems to inhibit
do get cancer.2014,6714,6722 Nonetheless, lots of research has evaluated shark cartilage angiogenesis.
as an anticancer agent. It turns out that shark cartilage does seem to inhibit b. An investigational
angiogenesis, the process required for new vasculature formation that feeds tumor shark cartilage
component, AE-
cells.6709 Shark cartilage powder has actually been studied in humans for a variety of
941, is showing
advanced cancers including lung,
prostate, breast, and colorectal cancers. But in each promise for some
case it was found
to be ineffective.2015,6716,6717,13086,17102 cancers.
c. Shark cartilage

Now researchers are looking at a particular component of shark cartilage called AE-941 powder in dietary
(Neovastat).
It's showing promise for renal-cell carcinoma and lung cancer. But at this supplements is
point it's still investigational. This isn't the same stuff that's in shark cartilage dietary INEFFECTIVE for

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supplements on store shelves. Tell patients to avoid shark cartilage dietary supplements. colorectal cancer.
d. All of the above
Hydrazine sulfate
is another "natural" product that people use to treat cancer. It's also
another supplement that cancer patients should avoid. Proponents claim that hydrazine View brands
containing:
sulfate improves appetite and shrinks tumors. But in the preliminary clinical trials that
have been published, it has been shown not to be effective for colorectal - Shark cartilage
cancer.8002,11767 Plus there are serious safety concerns. Hydrazine sulfate has been
linked to reports of liver toxicity, seizures, coma, and death.8005,10384,10385,11767 Steer
patients away from this one.

Colon Cancer Prevention    

Question #2
Hydrazine sulfate is
Nature
versus nurture is a long standing debate when it comes to causes of cancer. But inappropriate for
most of us recognize that it is usually a combination of both. There are certain lifestyle treating colon cancer
factors that we can adjust to reduce our risk of cancer. But there are some things we are because:
not in control of, such as family history. a. It doesn't seem to
be effective.
b. It seems to be
Risk Factors for Colorectal Cancer
unsafe.
Increased Risk c. It has poor
Non-modifiable Risk Factors Relative Risk* bioavailability.

Family History of colorectal cancer 1.8 d. Both A and B

(first degree relative)
Inflammatory Bowel Disease 1.5
Modifiable Risk Factors Relative Risk*
Obesity 1.5-2.0
Red Meat (> 7 servings/week vs. 1 1.5
serving/month)
Smoking 1.5
Alcohol (> 4 drinks/week vs. none) 1.4
Decreased Risk
Modifiable Risk Factors Relative Risk*  
Question #3

Physical activity 0.6 Which of the following

INCREASES the risk of
Vegetable/Fruit Consumption (> 5 0.7 colorectal cancer?
servings/day vs. < 3 servings/day)
a. Exercise
*Relative risk refers to the risk of colorectal cancer among people exposed to the
b. Obesity
risk factor compared to people who are not exposed to the risk factor.
Source: American Cancer Society 2005 c. High-fiber diet
d. Vegetable intake

A family history (e.g., parent, sibling) of colorectal cancer puts us at
the greatest risk. For
these patients, screening is vital, even at an early age.

Screening for Colorectal Cancer*

Yearly
Fecal occult blood test, or
Fecal immunochemical test
Every 5 years
Sigmoidoscopy, or  
Barium enema, or
CT colonography
Every 10 years
Colonoscopy

*Screen should start at age 50 for most people. For people at
high risk,
screening should begin earlier and can occur more
frequently.

Source: American Cancer Society 2010

Other risk factors can be changed by decreasing weight if overweight, quitting smoking,
and decreasing the amount of red meat and alcohol consumed.

The role of fiber, vegetables, and fruits is less certain. We used to be
fairly certain that
high-fiber diets DECREASED colon cancer risk. Researchers theorized that since high-
View brands
fiber foods such as wheat bran, barley, oats, psyllium, and oat bran
reduce the GI
containing:
transit time, they consequently reduce the gut's exposure
to ingested carcinogens...and
- Wheat bran
therefore reduce cancer risk. Some population studies supported this.
- Barley
- Oats

These studies showed a correlation between lower colon cancer risk and a
high-fiber,
- Blond psyllium
low-fat diet. But more recent evidence suggests that dietary fiber does NOT prevent the
- Oat bran
recurrence of colorectal adenomas, which are considered precursors to colorectal
- Lycopene
cancer.160,4819,4820,4821,5104,7585
Nonetheless, a high-fiber diet makes sense for most
- Sulforaphane
people. Most North Americans don't get enough dietary fiber to begin with. But it still
- Indole-3-carbinol

remains to be seen exactly what impact a high-fiber diet will have on the risk of

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developing colon cancer.

We also used to be fairly sure that a diet high in fruits and vegetables
would reduce
colon cancer risk. The thinking is that certain fruits and
veggies contain nutrients with
cancer-fighting components...lycopene in red fruits and vegetables; sulforaphane and
indole-3-carbinol
in broccoli, cauliflower, and other cruciferous vegetables; and

antioxidants. But some evidence suggests that eating lots of fruits and veggies might not
protect against colorectal cancer.12324 Like fiber, it still makes sense to aim for a diet
containing lots of fruits and vegetables. Even though we still aren't sure what impact it

will have on colorectal cancer, fruits and vegetables are good foods for
lots of other
reasons...and many of us don't get enough.

Several other approaches are also being investigated to reduce the risk of colon cancer.
Most approaches target a specific factor that may predispose patients to developing
colorectal cancer.

Polyp Reduction  

People
with adenomatous polyps in the colon have an increased risk of colorectal cancer.
One promising approach is to prevent early adenomas from progressing to cancerous
tumors.

Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen
(Motrin, Advil, Nuprin, etc.) and naproxen (Aleve, Naprosyn),
are enjoying an
unexpected role in this regard. There are reports that NSAID use can cut the death rate
from colorectal cancer by 40% to 50%.12326 Of course, this benefit has to be weighed  
Question #4
against the increased risk of GI bleeds due to NSAID therapy.
Which of the following is
TRUE?

Aspirin and NSAIDs inhibit the cyclooxygenase enzymes, COX-1 and COX-2. Current
a. Celebrex is FDA-
thinking is that COX-2 may be more important in colon cancer development than COX- approved for familial
1.12327 Researchers are finding that levels of COX-2 rise significantly in the GI tract in adenomatous
the presence of a malignancy. COX-2 seems to be important in helping the tumor build polyposis (FAP).
blood
vessels for continued growth.12328 Inhibiting COX-2 appears to cut off the tumor's b. Turmeric is an
blood supply.   effective alternative
to aspirin for

The COX-2 inhibitor Celebrex (celecoxib) has been approved by the
FDA to reduce the preventing colon
cancer.
number of polyps in patients with familial adenomatous polyposis (FAP), a rare condition
that significantly increases the risk of colorectal cancer. c. COX-1 levels are
elevated in patients
with colon cancer.

Some plant compounds might also inhibit the COX enzymes and have a role in reducing
d. All of the above
the risk of colorectal cancer. One example is turmeric. Turmeric seems to inhibit COX-2,
inhibit angiogenesis, and possibly induce apoptosis of cancer
View brands
cells.11138,11139,11140,11141,11142,12482 Turmeric looks promising, but it's too soon to
containing:
recommend to prevent colon cancer. - Turmeric

Practice Pearl
Tell patients to use turmeric cautiously if they are taking aspirin, NSAIDs,
warfarin, or other antiplatelet or anticoagulant drugs.
Turmeric seems to
decrease platelet aggregation and might increase the risk of bleeding if
combined with other antiplatelet drugs.11143

Bile Acids  

There's general consensus that secondary bile acids increase the risk of colon
cancer.12329,12330
Secondary bile acids are formed when bile acids secreted by the liver
are processed by anaerobic bacteria in the colon. Cholic acid, for example, is converted
to deoxycholic acid. Deoxycholic acid seems to trigger gene mutations that turn normal
cells into cancer cells.12331

There are three ways to disrupt this disease process. One is to reduce the amount of bile
acids released so fewer secondary bile acids are formed in the colon. There is some
evidence that estrogen works this way
to reduce colon cancer risk.12332 Some
investigators believe that cutting down on red meat can do the same, because meat
increases bile acids.

The second strategy is to decrease the number of anaerobes available to convert bile
acids to secondary bile acids. Some people think eating less animal fat will decrease the
number of anaerobes in the gut. But studies have produced conflicting data.2263

The third strategy is to disarm the secondary bile acids in the colon before they can do
harm. This can be done by binding them or reducing their concentration.

Ursodiol, a drug used for dissolving gallstones, reduces the colonic concentration of the
secondary bile acid deoxycholic acid. This may explain why new clinical research is
showing that ursodiol might protect
people with ulcerative colitis against colon
cancer.12333

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Calcium
has long been thought to reduce colon cancer risk. The theory is that calcium
might bind bile acids and other carcinogens in the intestine. Both DIETARY and
SUPPLEMENTAL calcium seem to help reduce colon cancer risk. Getting 1200 mg of
calcium from low-fat dairy food can interrupt the development of colon cancer at an early
stage...by keeping normal epithelial cells in the colon from proliferating abnormally.12334
View brands
There is also evidence that supplementing with calcium carbonate (1200 mg per day)
containing:
produces a moderate reduction in the recurrence of adenomas in people who have
- Calcium
already had a colorectal adenoma removed.970,994,1047,8820,12118,12120,15267
- Vitamin D

Vitamin D also seems to be important. People with below average vitamin D levels don't  
Question #5
seem to get any benefit from calcium.12118
Epidemiological evidence also shows that
The mechanism of
higher vitamin D serum levels,
as a result of increased vitamin D intake from food and
action of calcium for
supplements, increased sun exposure, and other factors, is associated with a reduced   reducing colon cancer

risk of cancer and cancer-related mortality in men. Men with the highest
level of vitamin risk is most similar to
D, corresponding to a 25 nmol/L higher serum concentration, have a 17% reduction in which of the following?
overall cancer incidence, 29% reduction in cancer-related mortality, 43% reduction in a. Hydrazine sulfate
gastrointestinal
cancer incidence, and 45% reduction in gastrointestinal cancer-related
b. Ursodiol

mortality.14320
c. Vitamin C

A clinical trial also shows that healthy postmenopausal women who take supplemental d. Turmeric
calcium 1400-1500 mg/day plus vitamin D3 (cholecalciferol) 1100 IU/day have a 60%
lower relative risk for developing cancer of any type.15629 This corresponds to a number
needed to treat (NNT)
of 25. To prevent one occurrence of cancer, 25 postmenopausal
women would need to receive this combination of calcium plus vitamin D for 4 years.

Consider calcium for people at high risk of colon cancer, especially patients with a
history of recurrent adenomas. Urge them to increase dietary intake of calcium from low-
fat products or advise them to take 1200 mg/day of elemental calcium...about the RDA
for most adult men and women. Suggest dividing the dose and taking it twice a day with
 
Question #6
meals to
improve absorption. Absorption is best if no more than 500 mg is taken at a
time. Which of the following
has been associated
with a reduced risk of

Advise patients to ensure that they get adequate intake of vitamin D. The current cancer of all types?
recommended daily allowance for vitamin D is 600 IU for most
adults.17506 But many
a. Hydrazine sulfate
experts now recommend higher doses, ranging from 800-2000 IU daily. The Canadian
Cancer Society recommends 1000 IU daily during the fall and winter for adults in b. Ursodiol
northern latitudes...and year round for those at risk for having low vitamin D levels.15632 c. Vitamin D
Ensuring adequate vitamin D from all sources might decrease the risk of all types of d. Turmeric
cancer including colon cancer.
View brands
containing:
Practice Pearl
- Olive oil
Calcium can interact with a number of drugs. Be sure to administer
fluoroquinolone and tetracycline antibiotics at least 2-4 hours before or
after calcium supplements. Just like calcium binds bile acids, it can bind
to these drugs and decrease their absorption.

There is preliminary evidence from population studies that olive oil
reduces levels of
deoxycholic acid in the colon. People who consume more olive oil in their diets seem to
have a lower risk of developing colorectal cancer.3362 Consider recommending that olive
oil be substituted for other oils in routine cooking and eating.

Controlling Gene Mutations that Lead to Cancer   View brands

containing:
- Folic acid
Folic acid
is getting a lot of attention for reducing colorectal cancer risk. The large
Nurses' Health Study shows a whopping 75% lower risk of colon cancer in women who
 
Question #7
take multivitamins containing 400 mcg/day of folic acid for 15 years.9326 In men, taking
250 mcg/day or more is also associated with a lower risk. Especially interesting is that Which of the following is
TRUE about folic acid?
the effect of folic acid seems to be even more prominent for women with a high risk of
colon cancer due to family history.9325,9326 a. It seems to reduce
colon cancer risks in
  both men and

Folate is necessary for DNA synthesis and repair.2139,2144 Researchers suspect it helps women.
prevent genetic mutations that can lead to cancer. b. It seems to be
more effective in

Advise people to take 400 mcg/day of folic acid. Recommend a multivitamin that women with a family
contains folic acid or foods that have folic acid added...cereal, bread, corn meal, pasta, history of colon
or rice. cancer.
c. It is involved in
DNA repair.
d. All of the above

Repairing Oxidative Damage that Leads to Cancer    

Question #8
Which of the following is
Oxidative
damage to DNA promotes the development of cancer. Therefore, antioxidants, associated with a
which counteract these effects, are often thought to play a
role in cancer prevention. decreased risk of
developing colon
cancer?
Vitamin C
is sort of the "gold standard" antioxidant vitamin. Many people take it
with the

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hopes of lowering their risk of cancer and other diseases. There is some evidence that a. Dietary intake of
vitamin C
increasing DIETARY vitamin C can reduce some
forms of cancer.10819,10821 But there is
no reliable evidence that vitamin C reduces colorectal cancer. A clinical trial shows that b. Vitamin C
supplements
taking vitamin C in combination with beta-carotene plus vitamin E does not significantly
reduce the risk of colorectal cancer.12185 Tell patients that there is no proof vitamin C c. Vitamin E
supplements
will prevent cancer.
d. None of the above
Vitamin E
is an antioxidant that gets promoted for virtually everything. Cancer is no
View brands
exception. The evidence for vitamin E and colorectal cancer is somewhat conflicting.
containing:
Population studies link vitamin E supplements to a
lower incidence of colorectal
- Vitamin C
cancer.1047 But large-scale, randomized, controlled trials indicate that taking vitamin E is
  - Vitamin E
NOT effective for preventing colorectal adenomas or decreasing the risk of developing
3955,12185,13036 - Lutein
colon cancer.
 
Question #9
Practice Pearl Which supplement is
Advise non-healthy patients (e.g., those with cardiovascular disease or correctly matched with
diabetes) to avoid vitamin E in doses of 400 IU/day or more. There is its mechanism of
action?
some evidence that these patients who take high doses of vitamin E have
an increased risk of heart failure and increased mortality from all a. Lutein <>
Controlling gene
causes.12185,13036
mutations
b. Olive oil <>
Lutein
is a carotenoid that you probably associate with eye health. But increasing Reducing
DIETARY lutein intake also seems to reduce colon cancer risk.3962
It's not known if secondary bile acids
taking lutein SUPPLEMENTS would have the same benefit. Tell patients they can find c. Vitamin E <>
lutein in spinach, broccoli, and kale and other green leafy vegetables. Cyclooxygenase
inhibition
d. None of the above

The Bottom Line    

Question #10
Which of the following
Reducing
modifiable risk factors is the key to reducing the risk of colorectal cancer. It would be appropriate
makes a lot of sense to urge patients to go easy on red meat and increase consumption to recommend to a
of vegetables, fruits, and fiber. Even though the evidence may be conflicting regarding patient who is
concerned about
fruits, veggies, and fiber, there are still plenty of good reasons to consume these foods.
colorectal cancer?

Calcium and vitamin D are also worth considering, not necessarily for preventing cancer, a. Turmeric
but for other reasons such as preventing osteoporosis. Suggest that most patients get   b. Shark cartilage
1200 mg/day of calcium and 800 IU of vitamin D...from food and/or supplements. c. Lutein
supplements

Suggest a daily multivitamin, particularly one that contains folic acid (400 mcg). This is d. A multivitamin
probably beneficial for both men and women, particularly if there is a family history of containing folic acid
colon cancer.

Print a Natural Medicines Comprehensive Database recommendation chart as a
reference for your practice site.

   
 

Recommendation Chart for Natural Medicines Used for
Colon Cancer *
Likely Possibly Insufficient Possibly Likely Unsafe
Safe Safe Evidence Unsafe Unsafe

Effective            

Likely            
Effective

Possibly - Calcium          
Effective - Folic acid
- Olive oil
- Vitamin D
 
Insufficient - Diindolylmethane - Turmeric        
Evidence - Indole-3-carbinol  
- Lutein
(dietary)
- Lycopene
- Sulforaphane
- Vitamin C
 
Possibly - Barley     - Hydrazine    
Ineffective - Blond psyllium sulfate
- Oat bran  
- Oats
- Vitamin E
- Wheat bran
 
Likely   - Shark        
Ineffective cartilage
 
Ineffective            

 KEY:

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Natural Medicines - Clinical Management Series: Natural Medicines

 Consider recommending this product.

 Don't recommend using this product.
 Recommend against using this product.

* These proposed recommendations are based solely on the Safety and Effectiveness
Ratings contained in Natural Medicines Comprehensive Database. This assumes use
of
high-quality, uncontaminated products and the use of typical doses. Keep in
mind that some
products are never appropriate for some patients due to
concomitant disease states, potential
drug interactions, or other clinical
factors. Use your clinical judgment before recommending
any product.

References
160 Anon.
Consensus statement on cereals, fibre and colorectal and breast cancers. Proceedings of the European
Cancer Prevention consensus meeting. Santa Margheritia, Italy, 2-5 October 1997. Eur J Cancer Prev 1998;7:S1-
83.
970 Baron
JA, Beach M, Mandel JS, et al. Calcium supplements for the prevention of colorectal adenomas. Calcium
Polyp Prev Study Group. N Engl J Med 1999;340:101-7.
994 Baron
JA, Tosteson TD, Wargovich MJ, et al. Calcium supplementation and rectal mucosal proliferation: a
randomized controlled trial. J Natl Cancer Inst 1995;87:1303-7.
1047 White E, Shannon JS, Patterson RE. Relationship between vitamin and calcium supplement use and colon cancer.
Cancer Epidemiol Biomarkers Prev 1997;6:769-74.
2014 Lane IW, Comac L. Sharks don't get cancer. Garden City, NY: Avery Publishing Group; 1992.
2015 Miller
DR, Anderson GT, Stark JJ, et al. Phase I/II trial of the safety and efficacy of shark cartilage in the treatment of
advanced cancer. J Clin Oncol 1998;16:3649-55.
2139 Ma
J, Stampfer MJ, Giovannucci E, et al. Methylenetetrahydrofolate reductase polymorphism, dietary interactions,
and risk of colorectal cancer. Cancer Res 1997;57:1098-102.
2144 Slattery ML, Schaffer D, Edwards SL, et al. Are dietary factors involved in DNA methylation associated with colon
cancer? Nutr Cancer 1997;28:52-62.
2263 Isselbacher
KJ, Braunwald E, Wilson JD, et al. Harrison's Principles of Internal Medicine. 13th Ed. New York, NY:
McGraw-Hill, 1994.
3362 Stoneham M, Goldacre M, Seagroatt V, Gill L. Olive oil, diet and colorectal cancer: an ecological study and a
hypothesis. J Epidemiol Community Health 2000;54:756-60.
3955 Greenberg
ER, Baron JA, Tosteson TD, et al. A clinical trial of antioxidant vitamins to prevent colorectal adenoma.
Polyp Prevention Study Group. N Engl J Med 1994;331:141-7.
3962 Slattery ML, Benson J, Curtin K, et al. Carotenoids and colon cancer. Am J Clin Nutr 2000;71:575-82.
4819 Alberts
DS, Martinez ME, Roe DJ, et al. Lack of effect of a high-fiber cereal supplement on the recurrence of
colorectal adenomas. Phoenix Colon Cancer Prevention Physicians' Network. N Engl J Med 2000;342:1156-62.
4820 Schatzkin
A, Lanza E, Corle D, et al. Lack of effect of a low-fat, high-fiber diet on the recurrence of colorectal
adenomas. Polyp Prevention Trial Study Group. N Engl J Med 2000;342:1149-55.
4821 Fuchs CS, Giovannucci EL, Colditz GA, et al. Dietary fiber and the risk of colorectal cancer and adenoma in women.
N Engl J Med 1999;340:169-76.
5104 Reddy BS. Role of dietary fiber in colon cancer: an overview. Am J Med 1999;106:16S-9S.
6709 Berbari
P, Thibodeau A, Germain L, et al Antiangiogenic effects of the oral administration of liquid cartilage extract in
humans. J Surg Res 1999;87:108-13.
6714 Natl Cancer Institute CancerNet. Cartilage website: www.cancer.gov (Accessed 18 August 2000).
6716 Leitner
SP, Rothkopf MM, Haverstick L, et al. Two phase II studies of oral dry
shark cartilage powder (SCP) in
patients (pts) with either metastatic breast or prostate cancer refractory to standard treatment. Proc Am Soc Clinical
Oncol 1998;17:A240.
6717 Rosenbluth
RJ, Jennis AA, Cantwell S, DeVries J. Oral shark cartilage in the treatment of patients with advanced
primary brain tumors. A phase II pilot study. Proc Am Soc Clinical Oncol 1999;18:A554.
6722 Mathews J. Media feeds frenzy over shark cartilage as cancer treatment. J Natl Cancer Inst 1993;85:1190-1.
7585 Bonithon-Kopp
C, Kronborg O, Giacosa A, et al. Calcium and fibre supplementation in prevention of colorectal
adenoma recurrence: a randomised intervention trial. European Cancer Prevention Organisation Study Group.
Lancet 2000;356:1300-6.
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