Cancer Treatment: The Critical Factors-4

Step Eight: Inhibiting Angiogenesis


How To Implement Step Eight
Angiogenesis, the growth of new vessels from preexisting blood vessels, is critical during fetal development but occurs minimally in healthy adults. Exceptions occur during wound healing, in inflammation, following a myocardial infarction, in female reproductive organs, and in pathologic conditions such as cancer (Shammas et al. 1993; Suh 2000).

Angiogenesis is a strictly controlled process in the healthy, adult human body, a process regulated by endogenous angiogenic promoters and inhibitors. Dr. Judah Folkman, the father of the angiogenesis theory of cancer, explains: "Blood vessel growth is controlled by a balancing of opposing factors. A tilt in favor of stimulators over inhibitors might be what trips the lever and begins the process of tumor angiogenesis."

According to the National Cancer Institute, solid tumors cannot grow beyond the size of a pinhead, that is, 1-2 cubic mm, without inducing the formation of new blood vessels to supply the nutritional needs of the tumor. Since rapid vascularization and tumor growth appear to occur concurrently, interrupting the vascular growth cycle is paramount to overcoming the malignancy.

Tumor angiogenesis results from a cascade of molecular and cellular events, usually initiated by the release of angiogenic growth factors. At a critical phase in the growth of a tumor, the tumor sends out signals to nearby endothelial cells to activate new blood vessel growth. The pro - angiogenic growth factors diffuse in the direction of preexisting blood vessels, encouraging development (Folkman 1992 b ; Folkman et al. 1992 a ).

Various agents are known to activate endothelial cell growth, including angiogenin, estrogen, interleukin-8, fibroblast growth factors (both acidic and basic), prostaglandin E2, tumor necrosis factor, granulocyte colony-stimulating factor, and VEGF. VEGF and basic fibroblast growth factors are expressed by many tumors and appear particularly important to tumor development and angiogenesis (NIH/NCI 1998)

A number of substances from orthodox and natural pharmacology (angiostatin, endostatin, interferons, interleukin-2, curcumin, green tea, lactoferrin, N-acetyl-cysteine (NAC), resveratrol, grape seed-skin extract, retinoic acid (vitamin A), and vitamin D) are anti - angiogenic in nature ( to read more about natural products with an anti - angiogenesis profile, please turn to the Cancer Adjuvant Therapy protocol). Endostatin, a fragment of collagen XVIII, and angiostatin, a fragment of plasminogen involved in the coagulation process, have produced remarkable results in animal models.

Anti-angiogenesis drugs approved by the FDA to consider include Avastatin® and thalidomide.


How to implement step Eight

There are clinical trials using other anti-angiogenesis agents. Call (800) 422-6237 or log on to www.cancer.gov/clinicaltrials to find out if you are eligible to participate.
In the Cancer Adjuvant Therapy protocol of this book, there are nutrients that have demonstrated potential antiangiogenesis effects such as green tea extract and curcumin. Refer to the Cancer Adjuvant Therapy protocol for information and dosing recommendations.

SUMMARY

1)Step One

2)Step Two

3)Step Three

4)Step Four

5)Step Five

6)Step Six

7)Step Seven

8)Step Eight

Implementing The Eight Steps
This protocol has described therapies that a leading-edge oncologist can prescribe to improve the odds of long-term survival and possible cure.

The fundamental message is to have your oncologist thoroughly assess the individual characteristics of your tumor, your blood system, and available treatments. Based on this evaluation, patients can interact with their oncologists to determine what therapies may work synergistically with standard conventional treatments.

The objective of this multimodality approach is to attack tumor cells where they are most vulnerable. The primary determining factor in choosing the specific drugs is finding the various tumor cell and blood tests recommended in this protocol, along with historical statistical data that can help ascertain how your tumor will respond to specific therapies.

The following summary is a succinct reiteration of the eight approaches discussed in this protocol:


Step One: Evaluating the Molecular Biology of the Tumor Cell Population

How to implement: Make certain your surgeon sends a specimen of your tumor to IMPATH (Telephone: (800) 447-5816, website: www.impath.com ) for immunohistochemistry testing, using the contact information just provided. You may have to pay out-of-pocket for this test.


Step Two: Analyzing the Patient's Living Tumor Cells to

Determine Sensitivity or Resistance to Chemotherapy

How to implement: Get in touch with Rational Therapeutics (Telephone: (562) 989-6455, website: www.rationaltherapeutics.com) using the contact information provided so that your surgeon can follow the precise instructions required to send a living specimen of your tumor for chemosensitivity testing. It is important that your surgeon carefully coordinate with Rational Therapeutics in order to ensure your cells arrive in a viable condition. You may have to pay for this test yourself because insurance may not reimburse you for it.


Step Three: Protecting Against Anemia

How to implement: If your hemoglobin or hematocrit levels are not in the optimal ranges, ask your physician to prescribe an individualized dose of Procrit.

In order for Procrit to effectively boost red blood cell production, it is essential that your body have adequate iron stores. Even if you have adequate iron stores prior to Procrit therapy, the rapid production of red blood cells induced by Procrit may deplete iron stores. Anyone using Procrit should have periodic assessment of their iron stores by means of a serum ferritin level. If less than 200, a soluble transferrin receptor (sTfR) level should be obtained. If evidence of iron deficiency is found, your physician will consider iron supplementation after ruling out excessive blood loss due to a variety of causes.

Dietary supplements that can help protect against anemia due to other causes include folic acid (800 mcg/day), vitamin B12 (500 mcg/day), and melatonin (3-10 mg/day, at night) (Vaziri et al. 1996; Herrera et al 2001).


Step Four: Inhibiting the COX-2 Enzyme

How to implement: Ask your physician to prescribe one of the following COX-2 inhibiting drugs:

Lodine XL, 1000 mg once daily, or
Celebrex, 100-200 mg every 12 hours, or

Step Five: Suppressing Ras Oncogene Expression

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

Lovastatin, 40 mg twice daily, or
Zocor, 40 mg twice daily, or
Pravachol, 40 mg once daily
Note: These statin drugs can produce toxic effects in a minority of patients. Physician oversight and monthly blood tests to evaluate liver function 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: 8-12 capsules of Mega EPA/DHA w/Sesame Lignans per day.
Green Tea Extract: two-three 725 mg capsules daily.
Garlic Extract: 3 tablets daily with meals.

Step Six: Correcting Coagulation Abnormalities

How to implement: Ascertain if you are in a hypercoagulable (prethrombotic) state by having your blood tested for prothrombin (PT), partial thromboplastin time (PTT), and D-dimers. A prethrombotic state is indicated by a shortening of PT and/or PTT and an increase in D-dimers.

If there is any evidence of a prethrombotic state, ask your physician to prescribe the appropriate individualized dose of LMWH. If you cannot afford LMWH, ask that lower-cost Coumadin be prescribed instead. Anticoagulation requires significant patient education and monitoring of laboratory tests to minimize the risks of hemorrhage due to overanticoagulation. As in all biological systems, a balance must be established if health is to be restored.


Step Seven: Maintaining Bone Integrity

How to implement: 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 bony metastasis occurs. An oral bisphosphonate drug to consider is Actonel at a dose of 30 mg twice a week or Fosamax at a dose of 70 mg once a week. Either drug must be taken at least 1 hour before breakfast and with water only. 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.

A newer, more potent IV bisphosphonate, Zometa, can be used at a starting dose of 1-2 mg for the first dose and then 4 mg every 3-4 weeks thereafter. Zometa is routinely given as a 15-minute infusion. 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 Restore provide optimal potencies of bone protecting nutrients. Some physicians also prescribe a synthetic vitamin D such as Calcitriol (Rocaltrol) or Hectorol.

Since excessive bone breakdown releases growth factors into the bloodstream that can fuel cancer cell growth, the DPD urine test (which can be ordered through the Life Extension Foundation (800)-208-3444) 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 like Bone Restoree to protect against excess bone deterioration.


Step Eight: Inhibiting Angiogenesis

How to implement: There are a number of clinical trials using anti - angiogenesis agents such as angiostatin. Call (800) 422-6237 or log on to www.cancer.gov/clinicaltrials to find out if you are eligible to participate. In the Cancer Adjuvant Therapy protocol of this book, there are nutrients that have demonstrated potential antiangiogenesis effects such as green tea extract and curcumin. Refer to the Cancer Adjuvant Therapy protocol for information and dosing recommendations. The drug Avastatin® is now approved, and may be considered as an anti-angiogenesis therapy against a variety of cancers.


Implementing the Eight Steps
As can be seen from the eight-step list, a patient might be prescribed several treatments in addition to standard therapy for the purposes of inhibiting the COX-2 enzyme, suppressing the r R as oncogene, protecting against anemia/hypercoagulation, inhibiting blood vessel growth in the tumor (angiogenesis), maintaining bone integrity, and so forth.

While these therapies are substantiated in the published scientific literature and most are part of mainstream medicine, few cancer patients are benefiting from this knowledge.

If you are determined to wage modern medicine against your tumor, some or all of these therapies should be considered, depending on your individual situation. The reader is advised to refer to the Cancer Adjuvant Therapy protocol for additional guidance. If standard therapies such as radiation or chemotherapy are being contemplated , please refer to the Cancer Surgery, Cancer Radiation and/or Cancer Chemotherapy protocols.

Product availability

Super EPA/DHA w/Sesame Lignans, Mega Green Tea Extract, Kyolic® Reserve Garlic Extract and melatonin, folic acid, vitamin B12, and Bone Restore are available by ordering on line

Staying Informed

The information published in this protocol is only as current as the day the manuscript was sent to the printer. This protocol raises many issues that are subject to change as new data emerge. Furthermore, cancer is still a disease with unacceptably high mortality rates, and none of our suggested regimens can guarantee a cure.

The Life Extension Foundation is constantly uncovering information to provide to cancer patients. A special website has been established for the purpose of updating patients on new findings that directly pertain to the published cancer protocols. Whenever Life Extension discovers information that may benefit cancer patients it will be posted on the website www.lefcancer.org.

Before utilizing the cancer protocols in this book, we suggest that you check www.lefcancer.org to see if any substantive changes have been made to the recommendations described in this protocol. Based on the sheer number of newly published findings, there could be significant alterations to the information you have just read.