Cancer Treatment: The Critical Factors-3

Researchers at Rutgers University investigated the ability of different green and black tea polyphenols to inhibit H-Ras oncogenes. The Rutgers team found that all the major polyphenols contained in green and black tea except epicatechin showed strong inhibition of cell growth (Chung et al. 1999). Texas A&M University also found that fish oil decreased colonic Ras membrane localization and reduced tumor formation in rats. In view of the central role of oncogenic Ras in the development of colon cancer, the finding that omega-3 fatty acids modulate Ras activation likely explains why dietary fish oil protects against colon cancer (Collett et al. 2001).

Statins are a class of popular cholesterol-lowering drugs. Mevacor (lovastatin), Zocor (simvastatin), and Pravachol (pravastatin) are statin drugs shown to inhibit the activity of Ras oncogenes (Wang et al. 2000). Statin drugs block the hydroxymethylglutaryl - coenzyme A (HMG-COA) reductase enzyme, which depletes cells of farnesyl pyrophosphate. Levels of total Ras do not decrease but rather shifts in when Ras protein occurs, that is, farnesylated Ras decreases and unmodified, non un farnesylated Ras increases (Hohl et al. 1995).

Illustrative of the potential of statin therapy, patients with primary liver cancer were treated with either the chemotherapeutic drug 5-FU or a combination of 5-FU and 40 mg/day of pravastatin. Median survival increased from 9 months, among patients treated with only 5-FU, to 18 months when using 5-FU combined with the statin drug pravastatin (Pravachol®). Increased survival was attributed to decreased cellular proliferation and incidence of metastasis (Wang et al. 2000).

If a statin drug is planned to be co - administered with chemotherapy, some patients are medicated cyclically, that is, 3 weeks of a statin drug such as lovastatin (80 mg/day) followed by a 2-week break before restarting the statin. Other regimens involve using the statin drug for 6 continuous months or until signs of toxicity develop.

Note: Some cancer patients may benefit from coenzyme Q10 supplementation when taking statin therapy. For a detailed explanation, please consult the Coenzyme Q10 section in the Cancer Adjuvant Therapy protocol.

Individuals with cancer should consider an immunohistochemistry test of their cancer tissue for mutated ras genes at GENZYME Laboratories ( see the beginning of this protocol ), a recommendation the Life Extension Foundation first made in 1997. The Life Extension Foundation strongly believes all cancer patients should undergo immunohistochemical testing to determine p53 and Ras status. As mentioned previously, the following laboratory can perform the test:

GENZYME Laboratories,
Telephone: (800) 447-5816


How to implement step fiVE

Ask your physician to prescribe one of the following statin drugs to inhibit the activity of Ras oncogenes:

Mevacor (lovastatin), 40 mg twice each day, or
Zocor (simvastatin), 40 mg twice each day, or
Pravachol (pravastatin), 40 mg once a day
Note: These statin drugs can produce toxic effects in patients. Physician oversight and careful surveillance with monthly blood tests (at least initially) to evaluate liver function, muscle enzymes, and lipid levels are suggested.

In addition to statin drug therapy, consider supplementing with the following nutrients to further suppress the expression of Ras oncogenes:

Fish Oil Capsules: 2100 mg of EPA and 1500 mg of DHA day (Six Super Omega-3 fish oil capsules provide this potency)
Green Tea Extract: 1400 mg of tea polyphenols a day (Two Mega Green Tea Extract Caps provide this potency)
Aged Garlic Extract: 2400 mg (Four Kyolic® Reserve capsules provides this potency)

Step Six: Correcting Coagulation AbnormalitiES

How to Implement Step Six

Both experimental and clinical data have shown that coagulation disorders are common in patients with cancer, although clinical symptoms occur less often. Many cancer patients reportedly have a hypercoagulable state, with recurrent thrombosis due to the impact of cancer cells and chemotherapy on the coagulation cascade (Samuels et al. 1975). Pulmonary embolism is a particular problem for patients with pancreatic and gastric cancer, cancer of the large bowel, and women with ovarian cancer (Cafagna et al. 1997). Thus, momentum is building for anticoagulant therapy through reports, the vast majority of which are derived from secondary analyses of clinical trials on the treatment of thromboembolism.

Research on low-molecular-weight heparin (LMWH), an anticoagulant, shows promise in regard to increasing cancer survival rates. Data comparing unfractionated heparin to LMWH indicate that LMWH is equally beneficial if not more beneficial to cancer patients in terms of survival. The improved life expectancy gathered from anticoagulant therapy is not solely a result of the reduced complications from thromboembolism, but also from enzyme interactions, cellular growth modifications, and anti - angiogenic factors (Cosgrove et al. 2002). It appears heparin inhibits the formation of cancer's vascular network by binding to angiogenic promoters, that is, basic fibroblast growth factor and VEGF (Mousa 2002).

Another important aspect of anticoagulant therapy involves breaking down fibrin, a coagulation protein found in blood. Fibrin has various strategies it employs to accommodate the tumor. For example, fibrin covers maverick cells with a protective coat, hindering recognition by the immune system. In addition, fibrin relays a signal to the cancer cell to start angiogenesis, the growth of new blood vessels. As fibrin encourages a healthy vascular network and tumor growth increases, it sets the stage for metastasis.

German scientists evaluated whether cancer fatalities in women with previously untreated breast cancer were reduced using LMWH therapy. The study showed that breast cancer patients receiving LMWH, compared to women receiving unfractionated heparin, had a lower rate of mortality during the first 650 days following surgery. The survival advantage was evidenced after even a short course of therapy (von Tempelhoff et al. 2000). In another study of 300 breast cancer patients, none of the trial participants developed metastasis while receiving anticoagulant therapy although 37 (12.3%) died from the disease (Wellness Directory of Minnesota 2002).

Similar advantages were evidenced among small cell lung cancer patients undergoing anticoagulant therapy in union with conventional treatments. When anticoagulants were a part of the program, subjects enjoyed a better prognosis, that is, greater numbers of complete responses, longer median survival, as well as better survival rates at 1, 2, and 3 years compared to patients denied treatment (Lebeau et al. 1994 ; ). See the following references, however ( however, see also Zacharski et al. 1984, 1987; Chahinian et al. 1989).


How to Implement Step Six

Ascertain if you are in a hypercoagulable state by having your blood tested for prothrombin time (PT), partial thromboplastin time (PTT), and D-dimers. A hypercoagulable state is suggested if the shortening of the PT and PTT are seen in conjunction with elevation of D-dimers ( see table on laboratory tests for hypercoagulability ).

If there is any evidence of a hypercoagulable (prethrombotic) state, ask your physician to prescribe the appropriate individualized dose of low-molecular-weight heparin (LMWH). Repeat the prothrombin blood test every 2 weeks to guard against overcoagulation. If you cannot afford LMWH, ask that lower-cost Coumadin be prescribed instead.

Step Seven: Maintaining Bone Integrity

How to Implement Step Seven
Some types of cancer (breast and prostate) have a proclivity to metastasize to the bone (Hohl et al. 1995; Wang et al. 2000). The result may be bone pain, which also may be associated with weakening of the bone and an increased risk of fractures (Spivak 1994; Caro et al. 2001).

Patients with prostate cancer have been found to have a very high incidence of osteoporosis or osteopenia even before the use of therapies that lower the male hormone testosterone (Cazzola 2000). In settings such as prostate cancer, when excessive bone loss is occurring, there is a release of bone-derived growth factors, such as TGF-beta - 1, which stimulate the prostate cancer cells to grow further (Samuels et al. 1975; Dunst et al. 1999). In turn, prostate cancer cells elaborate substances such as interleukin-6 (IL-6), which has as one of its main effects the further breakdown of bone (Cafagna et al. 1997; Mousa 2002). Thus, a vicious cycle results: bone breakdown, the stimulation of prostate cancer cell growth, and the production of interleukin IL -6 and other cell products, which leads to further bone breakdown ( see Figure 3 ).

The intravenous (IV) or oral administration of any of the drugs called bisphosphonates, such as Aredia (IV), Zometa (IV), and Fosamax or Actonel (oral), can be used to stop this vicious cycle. Such agents stop excessive bone breakdown (resorption) and favor bone formation (Zacharski et al. 1984; Zacharski 1987; Chahinian et al. 1989; von Templehoff et al. 2000). Administration of bisphosphonates should be accompanied by an adequate intake of a bone supplement that supplies all raw materials to make healthy bone. These include calcium, magnesium, boron, silica, and vitamin D.

The problem that prostate and breast cancer patients face is that bisphosphonate therapy is approved for treatment only after cancer cells have metastasized to the bone and become clinically apparent by a nuclear medicine bone scan. If bisphosphonates were administered to those with certain types of cancers, the risk of bone metastasis could be significantly reduced (Zurborn et al. 1982; Kohli et al. 2002). The Life Extension Foundation recommended bisphosphonate drugs (similar to those mentioned above) for certain types of cancer patients more than a decade ago. For many cancer patients, it would be ideal to continue bisphosphonate drug therapy a year or longer. Insurance companies, however, do not pay for bisphosphonates until after the cancer has metastasized to the bone.

Maintaining bone integrity may inhibit the growth of a wide range of cancers. Even when bone is broken down as a result of normal aging, the release of growth factors, such as interleukin IL -6 and transforming growth factor, can fuel tumor cell propagation.

Bisphosphonate class drugs, along with the appropriate mineral supplements and exercise to stimulate bone formation, can help to maintain bone integrity and, thus, save the lives of cancer patients.

The Life Extension Foundation strongly advises that the status of bone integrity should be evaluated periodically by means of a quantitative computerized tomography bone mineral density study called QCT. At the very least, this should be done annually. We prefer to use the QCT scan over the D E XA since the QCT is not falsely affected by arthritis or calcifications in blood vessels that are commonly seen in men and women in their 50s and over. It is fairly common to see patients with a normal D E XA scan and yet the QCT will be blatantly abnormal.

QCT sites possibly near you can be found via Mindways, Inc. at (877) 646-3929 or Image Analysis at (800) 548-4849.

Tests that assess bone breakdown are inexpensive and involve a random urine collection obtained in the morning at the time of the second voided specimen. One such highly accurate test of bone resorption is called DPD (deoxypyridinoline). This test provides information on excessive bone breakdown (resorption).

The deoxypyridinoline (DPD) cross links urine test can be ordered through the Life Extension Foundation by calling 1-800-208-3444.


How to implement step SEVEN

• If you have a type of cancer with a proclivity to metastasize to the bone (breast or prostate), ask your physician for a bisphosphonate drug before evidence of bone metastasis occurs. An oral bisphosphonate drug to consider is Actonel in the high dose of 30 mg twice a week. Alternatively, Fosamax can be used at a dose of 70 mg once a week. These agents should be taken on an empty stomach at least 1 hour and optimally 2 hours before breakfast. Some people experience gastroesophageal side effects from oral bisphosphonate drug therapy and prefer administration directly into the vein. An IV-administered bisphosphonate drug such as Aredia may be administered monthly beginning at 30 mg the first month, 60 mg the second month, and working up to 90 mg for subsequent months. Alternatively, Zometa can be given at a dose of 4 mg intravenously over 15 minutes every 3-4 weeks. When taking a bisphosphonate drug, it is important to take a wide array of bone-protecting supplements such as calcium, magnesium, zinc, manganese, and vitamin D3. Six capsules a day of a product called Bone Assure provides optimal potencies of bone-protecting nutrients.

• Because excessive bone breakdown releases growth factors into the bloodstream that can fuel cancer cell growth, the DPD urine test should be done every 60-90 days to detect bone loss. A QCT bone density scan should be done annually. If either of these tests reveals bone loss, ask your physician to initiate bisphosphonate drug therapy. Every cancer patient should take a bone-protecting supplement such as Bone Assure to protect against excess bone deterioration.