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Choosing the Best Chemotherapy Drugs to Kill Your Tumor

It is highly desirable to know what drugs are effective against your particular cancer cells before these toxic agents are systemically administered to your body. A company called Rational Therapeutics, Inc., performs chemosensitivity tests on living specimens of your cancer cells to determine the optimal combination of chemotherapy drugs.

Dr. Robert Nagourney, a prominent hematologist/oncologist, founded Rational Therapeutics, Inc., in 1993. Rational Therapeutics pioneers cancer therapies that are specifically tailored for each individual patient. They are a leader in individualized cancer strategies. With no economic ties to outside healthcare organizations, recommendations are made without financial or scientific prejudice.

Rational Therapeutics develops and provides cancer therapy recommendations that have been designed scientifically for each patient. Following the collection of living cancer cells obtained at the time of biopsy or surgery, Rational Therapeutics performs an Ex-Vivo Apoptotic (EVA) assay on your tumor sample to measure drug activity (sensitivity and resistance). This will determine exactly which drug(s) will be most effective for you. They then make a treatment recommendation. The treatment program developed through this approach is known as assay-directed therapy.

At present, medical oncologists, according to fixed schedules, prescribe chemotherapy. These schedules are standardized drug regimens that correspond to specific cancers by type or diagnosis. These schedules, developed over many years of clinical trials, assign patients to the drugs for which they have the greatest statistical probability of response.

Patients with cancers that exhibit multidrug resistance will likely receive treatments that are wrong for them. A failed attempt at chemotherapy is detrimental to the physical and emotional well being of patients, is financially burdensome, and may preclude further effective therapies.

Rational Therapeutics' EVA assay uses your living tumor cells to determine which drug or drug combination induces apoptosis in the laboratory. Each patient is highly individualized with regard to sensitivity to chemotherapy drugs. A patient's responsiveness to chemotherapy is as unique as their fingerprints.

Rational Therapeutics, leading the way in custom-tailored, assay-directed therapy, provides personal cancer strategies based on the tumor response in the laboratory. This eliminates much of the guesswork prior to the patient undergoing the potentially toxic side effects of chemotherapy regimens that could prove to be of little value against their cancer. Rational Therapeutics may be contacted at:

Rational Therapeutics, Inc.
750 East 29th Street
Long Beach, CA 90806
Telephone: (562) 989-6455; Fax: (562) 989-8160
Web site: www.rationaltherapeutics.com

In addition to the EVA chemosensitivity testing, we advocate immunohistochemistry testing of your tumor to provide additional data that will assist in making treatment decisions. The importance of the immunohistochemistry test is described in the Cancer Treatment: The Critical Factors protocol. The immunohistochemistry test can be done if your physician sends a specimen of your tumor to a specialty laboratory called  GENZYME  (www.genzymegenetics.com).  GENZYME can be reached by calling  (800) 447-5816 .  GENZYME also performs chemosensitivity testing of living tumors (fresh specimens). Because many chemotherapy patients' primary tumors were previously removed or irradiated,  GENZYME can perform the immunohistochemistry test with a frozen or parraffin-preserved tissue sample that is accessible through the pathology laboratory that examined your previous tumor(s).

Inhibiting the COX-2 Enzyme

Some progressive oncologists are prescribing cyclooxygenase-2 (COX-2) inhibitor drugs along with chemotherapy to improve the odds of successful treatment. COX-2 is an enzyme that many types of cancers use in order to propagate. COX-2 and its byproducts such as prostaglandin E2 (PGE2) have been shown to help fuel the growth of cancers such as colon, pancreas, estrogen-negative breast, prostate, bladder, and lung cancer.

Drugs that inhibit the cyclooxygenase enzyme are known as COX-2 inhibitors. Celebrex and Vioxx are two popular COX-2 inhibitors. Both Celebrex and Vioxx are nonsteroidal anti-inflammatory drugs (NSAIDs) that are usually prescribed to treat the symptoms of rheumatoid arthritis and osteoarthritis. There appears to be more research about Celebrex in the treatment of cancer than Vioxx.

Since chemotherapy can cause gastrointestinal bleeding, careful physician monitoring is needed when using a COX-2 inhibiting drug such as Celebrex. Caution is urged for those with known kidney disease, poor heart-lung function, liver disease, or susceptibility to stress-induced ulcers. The protocol entitled Cancer Treatment: The Critical Factors has a detailed description of the connection between COX-2 and cancer and why inhibiting the COX-2 enzyme is so important in treating many cancers.

In 1996, Life Extension recommended that most cancer patients take a COX-2 inhibiting drug because of solid evidence that cancer cells use the COX-2 enzyme to sustain their rapid division. In 1996, Americans had to import a COX-2 inhibitor named nimesulid from other countries because this class of drug was not widely available in the United States.

Experiments in laboratory animals suggest that drugs such as Celebrex could help cure cancer, especially if combined with chemotherapy or radiation (Hsueh et al. 1999; Pyo et al. 2001; Swamy et al. 2002). There are 100 separate cancer studies involving COX-2 inhibitors going on worldwide at this time.

Doctors are predicting that COX-2 inhibiting drugs may become standard therapy in 5-10 years. There was adequate evidence in 1996, however, to recommend COX-2 inhibiting drugs available to cancer patients. There are three potent COX-2 inhibiting drugs on the American marketplace. You may ask your physician to prescribe one of the following COX-2 inhibitors:

  • Lodine XL, 1000 mg once a day or
  • Celebrex, 200-400 mg every 12 hours or
  • Vioxx, 12.5-25 mg once a day

Controlling Cancer Cell Growth

A family of proteins known as ras oncogenes often governs the regulation of cancer cell growth. The Ras family is responsible for modulating the regulatory signals that direct the cancer cell cycle and rate of proliferation. Mutations in genes encoding Ras proteins have been intimately associated with unregulated cell proliferation, that is, cancer.

There is a class of cholesterol-lowering drugs known as statins that has been shown to inhibit the activity of Ras oncogenes. Some of these cholesterol-lowering drugs are lovastatin, simvastatin, and pravastatin (Ura et al. 1994; Narisawa et al. 1996; Tatsuta et al. 1998; Wang et al. 2000; Furst et al. 2002; van de Donk et al. 2002).

In advanced primary liver cancer (hepatoma or hepatocellular carcinoma), patients who received 40 mg of pravastatin survived twice as long compared to those who did not receive this statin drug (Kawata et al. 2001). Interestingly, statins are also associated with the preservation of bone structure and improvement in bone density (Edwards et al. 2000; 2001; Pasco et al. 2002).

Some types of cancer (breast and prostate) have a proclivity to metastasize to the bone (Waltregny et al. 2000; Pavlakis et al. 2002). This results in bone pain that also may be associated with weakening of the bone and an increased risk of fractures (Papapoulos et al. 2000; Plunkett et al. 2000). Patients with prostate cancer, for example, are found to have a very high incidence of osteoporosis even before the use of therapies that lower the male hormone testosterone (Berruti et al. 2001; Smith et al. 2001).

In prostate cancer, when excessive bone loss is occurring, there is a release of bone-derived growth factors, for example, TGF-b1 (transforming growth factor-beta 1), that stimulate the prostate cancer cells to grow further (Reyes-Moreno et al. 1998; Shariat et al. 2001). In turn, prostate cancer cells elaborate substances such as interleukin-6 (IL-6) that facilitates the further breakdown of bone (Paule 2001; Garcia-Moreno et al. 2002). Thus, a vicious cycle results: bone breakdown-stimulation of prostate cancer cell growth that results in production of IL-6 and other cell products, which leads to further bone breakdown. When there is a breakdown of bone, the growth factors released can fuel cancer cell growth. (All cancer patients should refer to the Osteoporosis protocol in order to optimally maintain bone integrity and prevent the release of these cancer cell growth factors. The Prostate Cancer protocol has an extensive discussion about the importance of maintaining bone integrity.)

As far as statin drug dosing, higher amounts than are required to lower cholesterol are suggested for a period of several months. Cancer patients, for instance, have used 80 mg a day of lovastatin (Mevacor). This should be considered during chemotherapy in some cases. A monthly SMAC/CBC blood test is also recommended while taking a statin drug to monitor liver function. A rare potential side effect that can occur with the use of statin drugs is a condition known as rhabdomyolysis in which muscle cells are destroyed and released into the bloodstream. If muscle weakness should occur, alert your doctor so you can have a creatine kinase (CK) test to determine if muscle damage has occurred.

Combining a COX-2 Inhibitor with a Statin Drug and Chemotherapy

Depending on the type of cancer, a logical approach would be to combine a statin (such as Mevacor) with a COX-2 inhibitor and the appropriate dosing of chemotherapy.

Mevacor augmented up to five-fold the cancer-killing effect of the COX-2 inhibitor Sulindac (Agarwal et al. 1999). In this study, three different colon cancer cell lines were induced to undergo apoptosis by depriving them of COX-2. When Mevacor was added to the COX-2 inhibitor, the kill rate increased five-fold.

Physician involvement is essential to mitigate potential side effects of these drugs. Those who are concerned about potential toxicity should take into account the fact that the types of cancers that these drugs might be effective against have extremely high mortality rates. Please note that the use of statin drugs and COX-2 inhibitors for cancer is considered an off-label use of these drugs. You may ask your doctor to prescribe one of the following statin drugs to inhibit the activity of Ras oncogenes:

  • Mevacor (lovastatin), 40 mg twice a day or
  • Zocor (simvastatin), 40 mg twice a day or
  • Pravachol (pravastatin), 40 mg once a day

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

  • Fish Oil Capsules: 2400 mg of EPA and 1800 mg of DHA a day.
  • Green Tea Extract: 1500 mg of tea polyphenols a day.
  • Aged Garlic Extract: 2000 mg a day.

Antioxidants and Chemotherapy

There is a controversy as to whether cancer patients should take antioxidant supplements at the same time that cytotoxic chemotherapy drugs are being administered.

Proponents of antioxidants point to human studies showing that antioxidant supplements protect healthy cells from the damaging effects of chemotherapy drugs. Chemotherapy drugs can cause lethal heart muscle damage in a small percentage of cancer patients. Antioxidants such as vitamin E, coenzyme Q10 (CoQ10), N-acetyl-cysteine (NAC), glutathione, retinoids, ginkgo biloba, and vitamin C have been shown to specifically protect against chemotherapy-induced heart muscle damage (Tajima 1984; Mortensen et al. 1986; Iarussi et al. 1994; De Flora et al. 1996; D'Agostini et al. 1998; Schmidinger et al. 2000; Agha et al. 2001; Prasad et al. 2001; Blasiak et al. 2002). Other antioxidants have been shown to protect kidneys, bone marrow, and the immune system against chemotherapy toxicity.

Those who argue against antioxidant supplementation during chemotherapy are concerned that antioxidants will protect cancer cells against free-radical-induced destruction. Chemotherapy drugs work by varying mechanisms to induce cellular death. Some chemotherapy drugs kill cells by inflicting massive free-radical damage, while other chemotherapy drugs interfere with different cellular metabolic processes in order to eradicate cancer cells (and healthy cells as well). Depending on the type of cytotoxic drug used, however, antioxidants may confer protection to cancer cells during active chemotherapy.

Cancer patients contemplating cytotoxic chemotherapy are thus faced with a dilemma. They can take antioxidant nutrients to protect their healthy cells against the toxic effects of chemotherapy, or they can avoid all antioxidants during chemotherapy to possibly improve the chances that the chemotherapy drugs will kill enough cancer cells to induce a complete response or cure.

To further complicate matters, certain supplements have proven mechanisms that could augment the cytotoxic efficacy of chemotherapy. For instance, curcumin has been shown to suppress growth factors that cancer cells use to escape eradication by chemotherapy drugs. (A complete description of curcumin's potential synergistic benefits with chemotherapy drugs appears later in this protocol.) The problem is that curcumin is also a potent antioxidant, and one recent animal study shows that curcumin could interfere with the cancer cell-killing effect of certain chemotherapy drugs. The scientists who authored this study pointed out that while curcumin has demonstrated potent effects in preventing cancer, its use during active chemotherapy is questionable because of its ability to protect cells against the type of molecular damage inflicted by these chemotherapy drugs (Somasundaram et al. 2002).

Critics of this study point out that the low dose of curcumin used in this animal study was adequate to provide antioxidant protection to the cancer cells but not high enough to suppress growth factors that enable cancer cells to escape regulatory control by the chemotherapy drugs. It was also pointed out that not all chemotherapy drugs kill cancer cells by generating free radicals. This means that curcumin may not hinder other chemotherapy drugs, as evidenced by remarkable tumor regressions found in other animal studies and human case histories.

Table 1: How Different Chemotherapy Drugs Kill Cancer Cells


Trade Name

Mechanism of Action

Chemotherapy drugs that kill cancer cells by inflicting free-radical damage:

Alkylating agents

Free-radical damage




Free-radical damage

Mitomycin C


Plant alkaloids

Free-radical damage



Chemotherapy drugs that kill cancer cells by other mechanisms:


Inhibition of DNA/RNA synthesis



(Analog of the vitamin folic acid)

Topoisomerase inhibitors

Inhibition of chromatin function



Inhibition of topoisomerase II
Inhibition of topoisomerase II
Inhibition of topoisomerase II
Inhibition of topoisomerase II
Inhibition of topoisomerase II
Inhibition of topoisomerase II
Inhibition of topoisomerase I
Inhibition of topoisomerase II
Inhibition of topoisomerase I
Inhibition of topoisomerase II
Inhibition of topoisomerase II
Inhibition of topoisomerase II
Inhibition of topoisomerase I

Microtubule inhibitors

Inhibition of chromatin function



Mitotic arrest through binding of
microtubules and spindle precursors
Mitotic arrest through binding of
microtubules and spindle precursors

Table 1 provides some understanding of the mechanisms of action of chemotherapy drugs. Based on this information, it might appear that one could make a determination as to whether to take antioxidants based on the type of chemotherapy drug(s) used. Regrettably, there are other pathways (in addition to those listed) by which chemotherapy drugs induce cancer cell apoptosis that could be interfered with by taking the wrong dose of antioxidants. As already indicated, it is not possible to reach a scientific consensus as to which option to choose, that is, antioxidants or no antioxidants during active chemotherapy. There are too many variables such as the type of cancer, category of chemotherapy drug(s), molecular makeup of the cancer cells, individual variability, etc., to provide a conclusive recommendation for or against antioxidant supplementation during chemotherapy.