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Natural Strategies for Support Before, During, and After Chemotherapy

Natural Strategies for Support Before, During, and After Chemotherapy

Chemotherapy is a broad term that means the use of one or more drugs in the treatment of cancer. For many people, the very thought of chemotherapy evokes horrific images of debilitating nausea, vomiting, diarrhea, and weakness. It's true that the benefits of chemotherapy come at a cost (see the list of side effects below). One of the problems with standard chemotherapy is that the drugs work by attacking cells that are actively dividing, whether they are cancerous or not. But certain normal cells including those that line the intestines, bone marrow, and hair follicles divide constantly, so they are more prone to damage by chemotherapy. Which side effects develop depends on many factors: the agents used, the combination of drugs, the dosage and timing of treatments, the patient's general health, and the history of prior chemotherapy.

Side Effects of Chemotherapy

Short-Term
  • Anorexia
  • Bladder inflammation
  • Bone marrow suppression
  • Confusion and short-term-memory impairment
  • Diarrhea
  • Fatigue
  • Hair loss
  • Infections
  • Muscle pain
  • Nausea
  • Nerve irritation
Longer-Term
  • Infertility
  • Persistent bone marrow suppression
  • Persistent fatigue
  • Secondary cancers
Good News

The good news is that there are natural measures to reduce the toxicity of chemotherapy. There have also been advances in treatment that have made most chemotherapy regimens less toxic and more tolerable than in the past.

Complementary natural medicines can help in three ways: by acting directly against cancer cells, by protecting and supporting normal cell function, and by reducing the risk of adverse effects of therapy. When selected carefully and used judiciously, natural medicine has been found to improve your chances for achieving the best possible outcome.

As detailed in Chapter 7, Battling Cancer Through Diet, the importance of high-quality nutrition in the battle against cancer cannot be overstated. Cancer patients who have higher nutritional status are not only more likely to fight off infections and recover from their illness but are also better able to tolerate chemotherapy and its side effects. The following dietary suggestions are especially important for anyone undergoing chemotherapy, especially the chemotherapy-treated patient suffering from anorexia (loss of appetite) or cachexia (severe muscle wasting).

Key Dietary Recommendations for Chemotherapy Support
  • Drink a high-protein smoothie once or twice daily (see page 153 for more information and pages 320-332 for delicious recipes). Smoothies can take the place of breakfast and can also be used as between-meal snacks.
  • Stay well hydrated and drink 18 to 24 ounces of fresh vegetable juice daily, which can be taken with food or better yet, take a midmorning juice break.
  • It may be necessary to eat small frequent meals (every 1 to 2 hours) rather than larger meals less often.
  • Use extra seasonings, spices, and flavorings to improve food's taste appeal. A higher sensitivity to the taste of food may cause them to taste flavorless or boring.
  • Avoid flavorings that are very sweet or very bitter.
  • Eat soft, moist foods like smoothies, bananas, brown rice, vams. and so on, and avoid hard, dry foods like cereals, crackers, and hard candies.
  • Take small bites and chew completely.
Antioxidants and Chemotherapy

One of the most controversial natural measures to support chemotherapy is the recommendation to use antioxidant nutrients during the active phase of the treatment. This issue was briefly discussed in Chapter 7, Battling Cancer Through Dier. While there is little concern with using antioxidant nutrients after the completion of a course of chemotherapy or radiation treatment, many oncologists fear that antioxidant nutrients may interfere with the effectiveness of conventional therapies. Is this fear valid? According to many experts, the answer is no. We prefer to simply say, since you can always find exceptions, that it depends upon the nature of the treatment and the antioxidant in question. The biggest issue is not whether to use an antioxidant, but rather which anrioxidant offers the greatest benefit and what dosage should be used.

Deciding to recommend any treatment or supplement for any condition is a balancing act of risk versus benefit. While there are many questions that beg to be answered in well-designed clinical studies, we believe that appropriate antioxidant support has virtually no risk, yet can produce significant benefits, as the majority of human studies have shown that patients treated with antioxidants during chemotherapy and/or radiation have been noted to tolerate standard treatment better, have a better quality of life, and, most important, live longer than patients receiving no supplements.

The issue of combining antioxidant therapy with conventional cancer therapy is being championed by many experts, including Kedar Prasad and his colleagues at the Center for Vitamins and Cancer Research at the University of Colorado Health Science Center's Department of Radiology in Denver. He has stated that the concerns over the use of high-dosage antioxidants during chemotherapy and radiation "are not valid." He feels that "high doses of multiple antioxidant vitamins, together with diet modification and lifestyle changes, may improve the efficacy of standard and experimental cancer therapies by reducing their toxicity on normal cells and by enhancing their growth-inhibitory effects on cancer cells."! We agree with him wholeheartedly.

How can antioxidants protect healthy cells and not cancer cells? The answer to this question is attributed to the fact that cancer cells actually increase the intracellular level of antioxidants beyond normal levels, resulting in increased expression of growth-inhibitory genes, reduced expression of growth factors, and increased cellular suicide (apoptosis). The initial protection offered by the antioxidants in cancer cells to chemotherapy and radiation becomes irrelevant to the mechanism of action of the chemotherapy drug or radiation. Antioxidant supplementation at the dosages we recommend offers about as much protection to the cancer cell as a bulletproof jacket would during a nuclear attack. In contrast, normal cells are able to utilize the antioxidant to protect against the toxicity and damage caused by standard cancer treatments.

Chemotherapy Supplementation Program

There are so many natural products that offer benefit in supporting the chemotherapy parient that it can be overwhelming. In order to provide you with the best possible support, we have supplied a basic supplementation program for chemotherapy followed by some specific recommendations based on the type of chemotherapy agent being used. (See Appendix E, page 338.)

The Importance of Fish Oil Supplements

Again, we cannot stress enough the importance of utilizing fish oil supplements rich in the omega-3 fatty acids EPA and DHA in cancer patients. Fish oil supplements boost immune function and prevent cachexia --the severe wasting syndrome in cancer. Fish oil supplementation benefits anyone taking chemotherapy, especially anyone re ceiving the drug doxorubicin. Not only has it increased survival time in humans and animals taking the drug, but there is considerable evidence in test tube studies that fish oils (especially DHA) increase the effectiveness of the drug. Use fish oil supplements at a daily dosage of 700 to 1200 mg of EPA and 400 to 700 mg of DHA.

Maitake MD-Fraction and PSK/PSP

The benefits of these natural immune enhancers derived from mushrooms were discussed in Chapter 8, The Super Eight: Fighting Cancer Through Key Natural Products. It is very important to choose one of these two products. Either can reduce the side effects of conventional chemotherapy and radiation while at the same time enhance the effectiveness of these treatments. For example, here are some of the results from studies with PSK:

  • A randomized study of 253 patients with surgically treated stomach cancer showed that adding PSK to standard chemotherapy (5-FU) significantly increased the five-year disease-free survival rate from 59 to 71 percent.
  • Two randomized studies showed statistically significant increases in survival when PSK was added to standard chemotherapy after complete surgical removal of primary tumors.In one of the trials, survival time more than doubled.
  • PSK used with radiation therapy in non-small-cell lung cancer in creased the five-year survival rate by 39 percent in stages I and II disease and by 22 percent in stage III disease, compared with 16 percent and 5 percent, respectively, in the groups that did not receive PSK.
  • PSK significantly increased the survival rate in women with breast cancer undergoing surgery and chemotherapy, compared with the control group receiving only conventional treatment. The women receiving PSK also showed no significant drop in their peripheral white blood cell and platelet counts.

The dosage for maitake MD-fraction is 1 mg per every two pounds of body weight, while the dosage for PSK or PSP is 3000 mg a day. Either should be taken on an empty stomach. Continue at this dosage until the cancer is in remission, then cut the dosage in half.

Curcumin or Quercetin?

Curcumin and quercetin share many common features (both are discussed in Chapter 8, The Super Light: Fighting Cancer Through Key Natural Products). The choice of which to use depends on the type of cancer or the chemotherapy agent.

Both curcumin and quercetin protect healthy cells against the harmful effects of radiation and chemotherapy agents without reducing the effectiveness of these therapies against cancer cells. In particular, curcumin has been shown to enhance the action of the chemotherapy drug cisplatin, while quercetin increases the therapeutic efficacy of busulphan, Adriamycin (doxorubicin), cyclophosphamide, gemcitabine, topotecan, and cisplatin.

When to Use Curcumin or Quercetin (with Chemotherapy)

TYPE OF CANCER/TREATMENT CURCUMIN QUERCETIN
Brain X
Breast X
Colon X
Leukemia X
Liver X
Lung X
Lymphoma X
Ovarian X
Prostate X
Skin X
Stomach X
Radiation Therapy
Head and neck cancers X
Others X
Type of Chemotherapy
Alkylating agents and platinum compounds X
Antimetabolites X
Antitumor antibiotics X*
Microtubule and chromatin inhibitors X
*Note: Do not use quercetin in colon cancer if being treated by antitumor antibiotics like doxorubicin (rarely used in colon cancer). Curcumin is the better choice.
Melatonin

Melatonin is a hormone secreted by the pineal gland, a pea-sized gland at the base of the brain. Melatonin is a popular dietary supplement for the treatment of jet lag and insomnia. But tantalizing new evidence suggests that melatonin may have some benefit as an adjunct to cancer therapy. It has been shown to inhibit several types of cancers in test tube and animal studies and appears to work by increasing the expression of the p53 gene (see page 20), which acts to reduce cell proliferation by literally signaling cellular suicide (apoptosis).

Melatonin may help regulate some of the immune system's signaling proteins, including interleukins and gamma-interferon, which work by increasing the ability of white blood cells to identify and destroy tumor cells. Evidence also suggests that melatonin reduces the toxicity and/or enhances the effectiveness of other chemotherapy agents. Melatonin should not be used in acute leukemias, children, or people taking antidepressant drugs, however.

In studies involving patients with metastatic solid tumors, melatonin has been shown to enhance the anticancer effects of certain chemotherapy drugs, including cisplatin, etoposide, interleukin-2, interferon, tamoxifen, and lupron, as well as radiation.It also may reduce cachexia. Studies have shown that patients taking melatonin (20 mg a day) had significantly less weight loss (3 kg vs. 16 kg) and a lower chance of disease progression (53 percent vs. 90 percent) compared with those treated with supportive care alone.

A randomized trial in patients with advanced non-small-cell lung cancer investigated the effects of adding melatonin (20 mg a day) to a regimen of cancer drugs (cisplatin and etoposide). In this study, 15 of 24 patients who received the melatonin were still alive after one year, compared with 7 of the 36 patients who received chemotherapy alone. There was some evidence that tumors in the melatonin group responded better to treatment, but the difference was not statistically significant. The melatonin group also had less nerve damage, cachexia, and bone marrow suppression.

In another study, 63 patients with non-small-cell lung cancer that was not responding to cisplatin therapy were randomized to receive either 10 mg a day of melatonin or supportive care alone. Patients receiving melatonin lived longer on average (6 months vs. 3 months) and were more likely to survive for one year (8 of 31 survived vs. 2 of 32).

Treatment with melatonin (20 mg a day) was also associated with greater one-year survival than supportive care alone in patients with brain metastases.24 Other studies have noted that melatonin increased survival in malignant melanoma and in patients with metastatic discase.A European study of 250 stage IV (advanced metastatic) cancer patients found that patients given 20 mg of melatonin daily along with standard chemotherapy had double the response rate and double the one-year survival rate of those given chemotherapy alone.

Melatonin also has benefits for people undergoing radiation therapy, according to preliminary evidence. In one human study, the effect of radiotherapy plus 20 mg a day of melatonin was compared with that of radiotherapy alone in 30 patients with brain cancer (glioblastoma).

Patients with this form of brain cancer generally live only about 6 months after diagnosis. But at the end of one year, 6 of the 14 patients receiving melatonin were still living, compared with just one of the 16 undergoing radiotherapy alone. The researchers also noted fewer side effects from radiation therapy in patients taking melatonin.

Proteolytic Enzymes in Herpes Zoster (Shingles): A Common Side Effect of Chemotherapy

Because of the immune-suppressing effects of chemotherapy, a common side effect is shinglesa painful rash of blisters that is due to the same herpes virus that causes chicken pox. After someone recovers from chicken pox, the virus remains quiet, or dormant, in nerves. The infection can reactivate for various reasons later in life.

Shingles symptoms are usually limited to a small area of the body. This area is usually a small strip of skin on one side of the chest or ab domen. In some cases, the face can be involved, and this may cause an eye infection. The first symptoms are usually related to sensation. People may experience pain, numbness, tingling, or itching, Pain usually occurs at some point, and can be quite severe. This is usually followed by the development of groups of blisters. The areas around the blisters are often quite painful. The pain can be severe and last for weeks. If the immune system is severely compromised, the infection can be very serious, causing infection in the liver, lungs, and brain.

Orally administered pancreatic enzyme preparations have been used in Germany in the treatment of shingles for over 30 years. Even in Germany, however, the standard treatment is now oral acyclovir. The positive results obtained in earlier studies with proteolytic enzymes led researchers to design a study to determine the effectiveness of enzyme therapy versus acyclovir (Zovirax) -a popular drug used to treat shingles and other herpes virus infections.

The study design was a double-blind, controlled, multicenter trial of 90 imununocompetent patients with herpes zoster. Patients were randomly assigned to receive either acyclovir (800 mg) or an enzyme preparation (120 mg trypsin, 40 mg chymotrypsin, and 320 mg papain) five times a day for a treatment period of 7 days. The parameters of pain and skin lesions were measured over 14 to 21 days. Resulis indicated na statistically significant difference in either parameter between the two groups, indicating that the enzyme preparation is as ettective as acyclovir. The proposed mechanism of action for the enzyme preparation was stimulation of the breakdown of immune complexes, as well as enhancement of immune function.

Hand-Foot Syndrome

Hand foot syndrome (also known as palmar-plantar erythrodysthesia) is an adverse reaction to chemotherapy characterized by reddening of the skin. Doxorubicin, cytarabine, docetaxel, and fluorouracil are the most frequently implicated agents. Although, as the name implies, it usually affects the hands and feet, it can also affect any area that is subjected to heat or pressure. The redness is often accompanied by blistering, pain, and swelling. Eventually, the affected skin peels off, as healthy skin underneath regrows. There is rarely any permanent scarring unless a secondary infection occurs.

Hand-foot syndrome usually appears after two or three cycles of chemotherapy, but it can occur sooner or later. It is graded according to severity:

Grade 1: Mild redness or peeling, not severe enough to interfere with usual activity.

Grade 2: Symptoms have a mild impact on daily activity.

Grade 3:Symptoms severe enough to interfere with walking and normal wearing of clothes.

Grade 4: Severe symptoms involving infections or the need for hospitalization.

It is important to recognize hand-foot syndrome early. Report any symptoms of tingling, numbness, or redness to your oncologist. Avoid any unusual trauma to the hands and feet, as well as to other pressure areas, such as the elbows and knees.

To minimize absorption of the drug into the skin, limit skin exposure to external heat for one day prior to each chemotherapy infusion and three to five days afterward. For example, avoid hot baths, saunas, and heated whirlpools. Don't wear any tight clothing that causes pressure on the skin. Reduce sun exposure and be sure to wear sunblock with a sun protection factor (SPF) of at least 15 whenever going outdoors.

To relieve symptoms of hand-foot syndrome, take cool baths or showers. Take vitamin B, at dosages of 50 mg twice daily and use aloe vera gel topically to speed healing. In severe cases, it might be necessary for your physicians to change the dosage or timing of chemotherapy to allow more recovery time.

Types of Chemotherapy

The hundreds of different chemotherapy agents available today can be divided into seven main categories:

  • Alkylating agents and platinum compounds
  • Antimetabolites
  • Antitumor antibiotics
  • Biological response modifiers
  • Hormones and hormone inhibitors
  • Microtubule inhibitors and chromatin function inhibitors
  • New-breed agents

How a chemotherapy drug is administered—by mouth or intravenously or through some other means depends on many factors. Some drugs can't be absorbed through the digestive system, or they may cause unacceptably severe side effects if taken orally. Another way to take cancer drugs involves use of a small catheter that's threaded through the arteries to reach the blood vessels feeding the tumor. The drug is delivered right to the cancer rather than having to circulate throughout the entire body. That means smaller doses can be given, with a lower risk of side effects. One

Chemotherapy Agents

CLASS (SUBCLASS) COMMON NAME TRADE NAME
Alkylating agents and platinum compounds altretamine Hexalen
BCNU Carmustine
busulfan Myleran
chlorambucil Leukeran
cyclophosphamide Cytoxan,Endoxan,Neosar
fotemustine Muphoran
iphosphamide Ifex
lomustine CCNU
melphalan Alkeran, L-PAM
nitrogen mustard (mechlorethamine) Mustangen
pipobroman Vercyte
procarbazine Matulane, MIH
streptozocin, streptozotocin Zanosar
temozolomide Temodar
thiotepa Thioplex
triethylenemelamine TEM
Platinum-containing compounds carboplatin Paraplatin
cisplatin Platinol, Platinol-AQ
Antitumor antibiotics actinomycin D Cosmegen
bleomycin sulfate Blenoxane
daunomycin daunorubicin, Cerubidine
doxorubicin Adriamycin, Doxil
epirubicin Ellence
idarubicin Idamycin
mitomycin,mitomycin-C Mutamycin
mitramycin Mithracin
Antimetabolites asparaginase Elspar
chlorodeoxyadenosine Leustatin
cytosine arabinoside Ara C, Cytosar-U
deoxycoformycin pentostatin Nipent
floxuridine 5-FUDR

Chemotherapy Agents (Continued)

CLASS (SUBCLASS) COMMON NAME TRADE NAME
Antimetabolites (cont.) fludarabine phosphate Fludara
fluorouracil 5-FU
gemcitabine Gemzar
hydroxyurea Hydrea
mercaptopurine 6-MP
methotrexate Folex, MTX
thioguanine 6-TG
Biological response modifiers alpha interfero Intron A, Roferon-A
bacillus Calmette Guerin BCG, TheraCys, TICE
erythropoietin EPO,Epogen, Pocrit
G-CSF Neupogen
GM-CSF Leukine, Prokine
interleukin-2 (IL-2) Aldesleukin,Proleukin
Hormones
Corticosteroids betamethasone sodium phosphate Adbeon, Celestone phosphate
cortisone acetate Cortisone, Cortone Acetate
dexamethasone Decadron
dexamethasone acetate Dalalone D.P.
hydrocortisone Hydrocortone
prednisolone Prelone
prednisolone tebutate Hydeltra-T.B.A.
Anticorticosteroid aminoglutethimide Cytadren
Estrogens chlorotrianisene Tace
diethylstilbestrol DES
estradiol Alora, Climara. Esclim, Estrace, Estraderm, Estradiol, Fempatch, Gynodiol, Vivelle
estradiol valerate Delestrogen, Dioval, EstroSpan, Valergen
estrogens, conjugated,equine Premarin
estrogens, conjugated, synthetic A Cenestin
estrogens, esterified Estratab, Menest

Chemotherapy Agents (Continued)

CLASS (SUBCLASS) COMMON NAME TRADE NAME
Estrogens (cont.) estropipate Ogen. Ortho-Est
ethinyl estradiol Estinyi
Estrogen/Progesterone combinations estrogens, conjugated/ Medroxyprogesterone acetate Premphase, Prempro
Progestins medroxyprogesterone acetate Amen,Curretab,Cycrin, Depo-Provera, Prodoxy-10,Provera
progesterone Crinone, Progestasert, Prometrium
/Antiestrogen anastrozole Arimidex
letrozole Femara
raloxifene Evista
tamoxifen Nolvadex
Progestin/Antiestrogen megestrol acetate Megace
Antiprogestin mifepristone Mifeprex
Testosterones fluoxymesterone Halotestin
testosterone Adroderm, Testoderm, Testopel, Testro
testosterone cypionate Andro-Cyp, Depotest, Virilon-Im
testosterone enanthate Adro LA, Delatestryl. Everone, Testro LA
Antitestosterones bicalutamide Casodex
flutamide Eulexin
goserelin Zoladex
ketoconazole Nizoral
leuprolide Lupron
nilutamide Anandron, Nilandron
Microtubule inhibitors docetaxel Taxotere
paclitaxel Taxol
rinorelbine Navelbine
vinblastine sulfate Velban
vincristine sulfate Oncovin
Chromatin function inhibitors etoposide Vespid, VP-16
irinotecan Camptosar

Chemotherapy Agents (Continued)

CLASS (SUBCLASS) COMMON NAME TRADE NAME
Chromatin function teniposide Vumon
topotecan Hycamtin
New-breed agents rituximab Rituxan
ST1571 Gleevec
trastuzumab Herceptin

promising technique involves binding chemotherapy drugs to antibodies, which attach themselves to cancer cells and deliver their drug payload directly to the tumor while sparing healthy cells from destruction.

How often you take chemotherapy drugs is also a complex decision. Typically a drug protocol involves cycles: You take the drug for a period of time (often three or four weeks), followed by a drug "holiday." Then the cycle starts again. A new strategy, "fractionated chemotherapy," involves smaller doses taken more frequently. This method appears to be equally effective, and usually people experience fewer and milder side cffects. A new science, chronotherapy, is exploring the optimum strategy for timing the administration of cancer drugs.

Alkylating Agents and Platinum Compounds

Alkylating agents and platinum compounds cause damage to cells by directly damaging DNA. The various alkylating agents and platinumbased drugs differ in their patterns of antitumor activity, sites of activity, and side-effect profiles. These highly reactive chemicals are very toxic to cancer cells, but they also damage normal cells. They are especially toxic to rapidly proliferating normal cells, such as bone marrow and the cells that line the gastrointestinal tract. Cyclophosphamide, the most widely prescribed alkylating agent, is used to treat Hodgkin's disease and other lymphomas, acute lymphocytic leukemia, and a variety of solid tumors.

Platinum compounds work in a slightly different way from alkylating agents, but the result is the same damage to DNA. These agents are most often used in the treatment of testicular cancer (in combination with bleomycin and vinblastine), bladder cancer, head and neck cancer (with bleomycin and Auorouracil), ovarian cancer (with cyclophosphamide or doxorubicin),and lung cancer (with etoposide or Taxol). Gisplatin causes side effects, and its use today is limited to a few specific types of or as an alternative if cancer recurs after other forms of treatment been tried. A newer platinum compound, carboplatin, is becoming we widely used because it has a more favorable side-effects profile.

TOXICITY AND SIDE EFFECTS| The biggest problem with alkylating agents is bone marrow suppression. The bone marrow is responsible for manufacturing white and red blood cells and platelets. When the marrow is suppressed, you may experience low white cell counts and anemia. Signs and symptoms include fatigue, greater susceptibility to infections, especially yeast infections (candidiasis, also known as thrush), shingles, and slow healing. Your physicians will want to monitor your blood cell and platelet counts carefully during therapy with these drugs.

Platinum compounds pose many of the same risks. Besides suppression of bone marrow function, the biggest concern about use of cisplatin is toxicity to the kidneys. Other complications include severe nausea and vomiting (in virtually all patients), damage to the car drums (ototoxicity) leading to hearing loss, heart damage, hair loss, allergic reactions, and peripheral nerve damage (feelings of pins and needles or loss of feeling or pain in the hands or feet). Some patients experience changes in their sense of taste or color perception. Carboplatin is less toxic to nerves and kidneys and causes less nausea and vomiting, although it is more likely to suppress bone marrow. Some patients de velop allergic (rashlike) reactions.

WHAT TO DO IF YOU TAKE ALKYLATING AGENTS|For natural support when you are taking alkylating agents, as well as dealing with bone marrow suppression, we recommend utilizing the basic guidelines on diet given on page 238, as well as those described in Chapter 7. Battling Cancer Through Diet, and the chemotherapy supplement program listed in Appendix E on page 338. We also recommend the use of hydrotherapy at home, acupuncture, and Polyerga (a special spleen extract from hogs; for more information, see page 181). In one doubleblind, placebo-controlled study, Polyerga was shown to work in patients with head and neck cancers who were receiving 5-FU and cisplatin. These drugs typically cause a decline in the number of white blood cells called lymphocytes, but use of Polyerga stabilized lymphocyte levels. In

Warning

The anemia that develops as an adverse event of cancer chemotherapy is rarely due to low levels of iron. Unless blood tests such as serum fertitin show that you have an iron deficiency, do not take supplemental iron Too much iron in the blood can promote tumor growth and worsen the side effects of chemotherapy. Consult your physician before taking an iron supplement for anemia.

contrast, the placebo group did experience a drop in lymphocyte counts. The Polyerga group also reported less fatigue and higher energy levels than the placebo group, and there was no weight loss. In addition to the goal of boosting white blood cell counts, preventing weight loss is a major goal in the support of cancer patients, since weight loss reduces the tolerance to anticancer drugs, alters the functioning of the immune system, and can be a cause of death. For people of up to 140 pounds body weight, take one Polyerga tablet three times a day. For every additional 40 pounds body weight, add an additional tablet (e.g.. a 220-pound person would take 5 tablets daily in divided dosages). For best results, take Polyerga on an empty stomach before meals. Also, do not take Polyerga at the same time you take digestive enzymes such as pancreatin, bromelain, or papain.

Keep in mind that chemotherapy will almost always cause some drop in blood counts. The goal is to prevent such a severe drop that complications ensue. If the natural methods are not adequate, it's reassuring to know that modern medicine can offer some very effective treatments to help with low blood counts. These are bioengineered versions of growth factors normally made in the body. Erythropoeitin (EPO) stimulates the growth of red blood cells, and Neupogen stimulates the growth of white blood cells. These compounds have some drawbacks. They must be injected daily for up to five days; many people dislike having to administer injections to themselves. The other disadvantage is cost. A series of injections can cost thousands of dollars.

WHAT TO DO IF YOU TAKE PLATINUM COMPOUNDS |For protection when taking cisplatin or carboplatin, follow the basic dietary program given in Chapter 7 as well as the chemotherapy supplement program given hove. We especially recommend being sure to get appropriate levels of Vitamin C (500 mg three times daily), vitamin E (400 to 800 TU daily), selenium (100 to 400 mcg daily), and melatonin (20 mg daily at bedime) to enhance the effects of cisplatin and reduce its toxicity.

Selenium supplementation alone has been shown to be of value, but as we have stated repeatedly, when using antioxidants be sure they are used along with other antioxidants. In a study of patients given cisplatin alone or cisplatin plus selenium, white blood cell counts were significantly higher and fewer transfusions were needed during the cycles in which selenium was used. The same study found that blood markers that indicated kidney damage were lower in the selenium group. Animal studies have concluded that administering selenium with cisplatin allows larger doses to be used, resulting in better therapeutic efficacy with less toxicity. We also recommend increasing the consumption of soy foods. The soy isoflavonoid genistein increases the uptake of cisplatin into cancer cells. In one study, genistein was able to reestablish the effectiveness of cisplatin in ovarian cancer cells that had developed resistance to the drug.

CAUTIONS WHEN USING PLATINUM-BASED DRUGS |Do not take N-acetylcysteine (NAC), a derivative of the naturally occurring amino acid cysteine. Some people use NAC as a nutritional supplement to boost glutathione levels. However, two laboratory studies have shown that NAC inhibits the antitumor activity of cisplatin.In fact, we recommend that you avoid NAC during active treatment with any chemotherapy agent. After your treatment is complete, NAC may be of benefit--for example, by helping reverse kidney damage.

Also, avoid dosages of vitamin B6 over 200 mg a day. At higher levels, B6 may interfere with platinum-containing compounds.

Antitumor Antibiotics

The antibiotics you take to treat an infection are designed to attack and destroy bacteria, the one-celled creatures that make you sick. In cancer treatment, certain drugs can also be used to attack cancer cells. These drugs, known as antitumor antibiotics, work by binding directly to DNA components in the nucleus, thus interfering with DNA synthesis

A Special Licorice Extract Helps Mouth Ulcers

A special extract of licorice root can be extremely helpful in healing mouth ulcers that are often experienced by people on chemotherapy The extract is known as DGL. That's the abbreviation for deglycyrrhizinated licorice, but we like to think it stands for "darn good licorice." DGL is produced by removing glycyrrhetinic acid from concentrated licorice. This compound can result in elevations in blood pressure because of sodium and water retention. Yes, eating too much licorice candy, if it contains real licorice extract, can raise blood pressure. Because the glycyrrhetinic acid has been removed, DGL does not raise blood pressure.

In addition to having shown clinical benefit in healing mouth ulcers, DGL is also extremely useful in treating peptic ulcers (gastric or duodenal ulcers). In fact, in several head-to-head studies, DGL has been shown to be more effective than Tagamet, Zantac, or antacids in both short-term treatment and maintenance therapy of peptic ulcers.3940 Rather than inhibit the release of acid, DGL stimulates the normal de fense mechanisms that prevent ulcer formation, whether in the mouth, stomach, or intestines. It improves both the quality and quantity of the protective substances that line the intestinal tract, increases the life span of the intestinal cell, and improves blood supply to the intestinal lining. There is also some evidence that it inhibits growth of H.pylori, the bacterium that is linked to peptic ulcer disease and stomach cancer.

The standard dosage for DGL is one or two chewable tablets containing 400 mg DGL taken between meals or 20 minutes before meals. You won't get good results if you take DGL after meals. For DGL to be effective, it must mix with saliva. Taking DGL in capsules doesn't work: In order for it to be effective, it must mix with saliva. If your mouth is too sore to chew the tablets, let them dissolve in your mouth, or you can crush them and dissolve them in water.

A number of studies have shown that CoQ10 prevents the cardiac toxicity associated with antitumor antibiotics like doxorubicin. A small study in humans showed CoQ10 administration at 1 mg per kg (2.2 pounds) body weight led to 20 percent or greater reduction in heart damage compared with patients who took doxorubicin alone. DiarThea and mouth ulcer formation were also significantly reduced. In a study of 20 leukemia patients undergoing treatment with daunorubicin (a drug similar to doxorubicin), taking 100 mg of CoQ10 twice daily significantly reduced adverse cardiac events as measured by echocardiography. A study in mice also suggested that CoQ10 might enhance the antitumor activity of doxorubicin. CoQ10 has demonstrated other anticancer effects, including some positive results in preliminary human studies.

Another useful strategy is to take melatonin. In one study, melatonin (20 mg a day at bedtime) normalized platelet counts in 9 of 12 breast cancer patients who developed thrombocytopenia (reduced platelet counts) during treatment with epirubicin. In 5 of the patients, the tumors regressed in size. Melatonin has also been shown to increase the tumor-killing action of doxorubicin while simultaneously reducing undesirable toxic side effects.

Vitamin E may also reduce the toxicity of doxorubicin and may enhance the drug's anticancer effects. A study showed that giving mice vitamin E before administering the drug at lethal dosages reduced the death rate from 85 percent to 10 percent. This dose of vitamin E did not alter the suppression of tumor cell DNA synthesis by doxorubicin, however. The mice who got vitamin E lived longer on average than those treated with doxorubicin alone. The authors theorized that the vitamin E prevented heart damage by blocking oxidation of lipid molecules without impairing the drug's antitumor effects. In an animal study, vitamin C also has been shown to reduce the toxicity of doxorubicin without diminishing its effectiveness.

While quercetin has shown an ability to increase the concentration of doxorubicin in human breast cancer cells, it reduced concentrations in a colon cancer cell line . Therefore, use it if you have breast cancer, but do not use quercetin with doxorubicin if you have colon cancer; use curcumin instead. Curcumin has shown good inhibition of colon cancer in experimental studies and has also been shown to protect the heart and the kidneys from doxorubicin toxicity.

Studies in mice have shown that green tea increased doxorubicin concentrations in two types of tumors but not in normal tissue. The antitumor activity of the drug was enhanced 2.5 times in mice fed green tea. Another report confirmed these results showing that the tumor inhibition of doxorubicin increased from negligible to 62 percent. This report suggested that the activity of green tea was due to an amino acid, thea nine, rather than its flavonoid content. This association was solidined in several other studies, indicating that regular green tea consumption or the use of green tea extracts that contain theanine is preferable to polyphenol extracts in this application. The protocol for supplements to take to support antitumor antibiotic therapy appears on page 339.

Antimetabolites

Antimetabolites are compounds that interfere with the production of genetic material or another key aspect of cellular reproduction. There are three main categories of antimetabolites, each with different activity:

  • Antitolates, such as methotrexate (Folex, Mexate); these block folic acid, an essential component of enzymes that help manufacture DNA and RNA.
  • Purine analogs, such as mercaptopurine (6-MD, Purinethol) and thioguanine (6-TG); these block cellular growth and reproduction by interfering with the purine compounds xanthine and guanine, respectively, which are necessary for the manufacture of DNA and RNA.
  • Pyramidine analogs, such as 5-Huorouracil (5-FU, Adrucil) and fluorodeoxyuridine (FdUrd) (FUDR); these inhibit the manufacture of pyramidines, the other building blocks of DNA and RNA.

Antimetabolites, alone and in combination with other chemotherapy agents, are used in the treatment of many types of cancer, including cancers of the breast, lungs, livet, gastrointestinal tract, bone, ovaries, and pancreas, as well as certain leukemias and lymphomas.

TOXICITY AND SIDE EFFECTS| The toxicity of antimetabolites is somewhat less severe than other classes of chemotherapy agents. The most common side effects are bone marrow suppression (except floxuridine and asparaginase), mouth sores, hair loss, loss of appetite, nausca, and diarrhea. In fact, the presence of these side effects is often used as gauge that a sufficient dose has been given.

WHAT TO DO IF YOU TAKE ANTIMETABOLITES |These drugs can produce the same side effects as other chemotherapy drugs but usually in less severe forms. Follow the basic dietary program on page 238, as well as those described in Chapter 7, Battling Cancer Through Diet, and the chemotherapy supplement program given in Appendix E on page 338. There are some additional cautions worth noting:

The antimetabolite drug methotrexate (MTX) works by inhibiting the transformation of folic acid into compounds necessary for the replication of DNA. For this reason, patients should avoid taking large doses of folic acid while being treated with MTX. But folic acid is still an important nutrient for support of normal cell function. To err on the side of caution, we advise using no more than 800 mcg of folic acid daily during treatment with MTX. Between courses of MTX therapy, it is safe to take larger doses of folic acid if prescribed by your physician.

It is very important for people on MTX therapy to take whey protein. One of the key amino acids in whey protein, glutamine, increases the intratumor levels of MTX in human and rat studies, thereby increasing its cancer-killing effect.Within 24 hours, the rats who were given glutamine had a higher rate of tumor destruction. This result was due to the effect that glutamine exerts in decreasing the intratumor levels of glutathione, making tumors more susceptible to the MTX. For more information on this action of glutamine, see page 154. Again, we prefer whey protein over glutamine. Two servings of a whey protein smoothie, each providing 20 to 30 g of whey protein, are recommended.

Be aware that some common medications can interact with MTX. For example, aspirin and other anti-inflammatory agents can reduce the elimination of MTX through the kidneys, which thus increases blood levels and may lead to higher risk of toxicity. Penicillin can also produce a similar effect and should be avoided during treatment. Be sure all your physicians are aware of what drugs you're taking to reduce the risk of such interactions.

Biological Response Modifiers

Biological response modifiers are compounds that affect the way the body's immune system reacts to cancer. Examples include interferons and interleukins, which work directly by slowing down cancer cell reproduction. They also act indirectly by signaling white blood cells to atrack infecting organisms and cancer cells. The agent BCG works indirectly to enhance immune function. BCG is a live bacterial strain that is injected directly into tumors (usually of the bladder). White blood cells rush to the area of injection to kill the bacteria, and in their heightened state these immune cells kill the cancer cells as well.

Among the newest biological response modifiers are various growth factors. These work by overcoming the suppression of bone marrow that results from some forms of cancer treatment, thereby stimulating the bone marrow to manufacture blood cells. Erythropoietin is used to replenish red blood cells, while granulocyte-macrophage colony stimulating factor (GM-CSF sold as Leukine or Prokine) and granulocyte colony stimulating factor (G-CSF, sold as Neupogen) are used to replenish white blood cells. Positive benefits include decreasing the frequency of infections and shortening the stay in the hospital.

The use of biological response modifiers in cancer therapy is gaining acceptance, but treatment with these agents can be very expensive.

TOXICITY AND SIDE EFFECTS |The toxicity of biological response modifiers, especially the bone marrow stimulators, is generally low compared with other chemotherapy agents. But they can still produce significant side effects, including flu-like symptoms (fever, chills, muscle aches, headache, fatigue, and joint pain).

WHAT TO DO IF YOU TAKE BIOLOGICAL RESPONSE MODIFIERS |As with all forms of chemotherapy, follow the basic dietary program on page 238, as well as those described in Chapter 7. Battling Cancer Through Diet, as well as the basic chemotherapy supplementation program given in Appendix E on page 338. Patients who are taking interleukin-2 (IL-2) should supplement with melatonin. One study found that melatonin (40 mg a day) increased the effect of IL-2 against a variety of solid cancers. Another found that the combination of melatonin (40 mg a day) and IL-2 was a more effective treatment than cisplatin and etoposide in non-small-cell lung cancer?

Hormones and Antihormones

Hormones are chemicals your body produces to signal other organs to function. Some cancer tumors respond to the presence of hormones, so treatment with hormonal agents can alter tumor activity. Antihormones block the effect of the corresponding natural hormone on the cancer cells. For example, antiestrogens are used against estrogen-dependent breast cancers, while antitestosterones are used against testosterone dependent prostate cancers. Another type of hormone, the corticosteroids, are used primarily to suppress white blood cell growth in certain leukemias and lymphomas. The most commonly used corticosteroid is prednisone.

One of the more controversial antihormones is tamoxifen, which can prevent breast cancer in high-risk individuals and can reduce the risk of recurrence in women who have already had the disease. Tamoxifen has been used for more than 20 years. Here's how it works:

The surfaces of certain tumor cells have unique molecules, called receptors, that bind with molecules of estrogen. When that connection is made, it generates signals that tell the cancer cell to divide and thus causes the tumor to grow. Such cancers are described as estrogenresponsive tumors. Like estrogen, tamoxifen also binds with the estrogen receptor, but unlike the hormone, it does not trigger growth signals. When tamoxifen occupies the parking space," estrogen can't bind to the receptor. Thus the cancer cells grow more slowly, or they stop growing altogether. Studies indicate that tamoxifen lowers cancer risk by about half. That is, a woman who has a 50 percent chance of breast cancer recurrence without the drug might have only a 25 percent chance if treated with tamoxifen.

In women who have not yet gone through menopause, most of their estrogen is produced by the ovaries. After menopause (or following surgical removal of the ovaries), estrogen levels fall, but some estrogen is still produced by other metabolic systems, such as the aromatase enzyme system, which converts other hormones into estrogen. There are antiestrogen drugs available, such as Arimidex and Femara, that inhibit the aromatase system. They can be used alone or in combination with tamoxifen to reduce estrogen activity in cancer calls. Recent studies suggust that aromatase inhibitors may be as effective as tamoxifen and have fewer side effects, but these drugs do not yet have the long-term track record of tamoxifen.

Like breast cancer in women, prostate cancer in men is a hormone ponsive cancer. The hormone involved here is testosterone. Prostate cancer cells bind with testosterone, which triggers cell activity and growth. Drugs are available that affect testosterone production or metabolism. Leuprolide (Lupron) and goserelin (Zoladex) both work by blocking signals from the pituitary gland that tell the testicles to make testosterone. Drugs such as bicalutamide (Casodex) and futamide (Eulexin) act the way tamoxifen does: They block the hormone receptors on the surface of prostate cancer cells.

One drawback of treatment with antitestosterone agents is that prostate cancer cells may become resistant to hormone blockade-they figure out how to grow and divide without depending on signals from testosterone. If that happens, the disease can become much more difficult to treat. As a countermeasure, physicians may recommend intermittent hormone blockade. In this approach, the patient takes antihormones until the cancer appears well controlled, then stops treatment until the PSA levels rise. (PSA, or prostate specific antigen, is a protein released by prostate tumors that can be measured to evaluate the extent of the disease; see page 22 for more information.)

Another approach is known as triple hormone blockade. In this strategy, the patient takes a combination of Lupron, Casodex, and Proscar to inhibit the three major ways testosterone can affect the prostate. After about 13 months, most patients are able to discontinue treatment, taking only Proscar as maintenance therapy. This approach avoids the side effects of radiation and surgery and also minimizes the side effects of hormone blockade, because the treatment period is relatively brief. An analysis of 110 patients treated with this protocol and followed for as long as 10 years found that all patients were off therapy and that none had to be re-treated.

TOXICITY AND SIDE EFFECTS Hormonal agents are generally well tolerated and usually do not produce severe toxicity. Side effects tend to be more annoying than debilitating.

ANTIESTROGEN AGENTS |Common side effects include nausea, vomiting, indigestion, and hot flashes. Some patients may experience mild bone marrow suppression. These complications tend to appear in the first few weeks of therapy and disappear fairly soon (although some women experience hot flashes for as long as they take tamoxifen).

Less common adverse reactions include depression, tiredness, dizziness, bone pain, and reduced sex drive. Rare side effects include:

  • Allergic reactions, such as skin rashes
  • Temporary thinning of the hair
  • Headaches (including changes in patterns of migraines)
  • Flaking fingernails (usually occurring only after years of treatment)
  • Thrombosis (blood clots)
  • Visual problems (blurred or reduced vision)
  • Endometrial hyperplasia and cancer

Women taking tamoxifen who have not yet reached menopause may notice changes in their monthly periods. Menstrual flow may become irregular or lighter; sometimes it stops altogether. Some women report vaginal discharge or itching in the vulva.

Thrombosis is particularly serious, since blood clots can block blood vessels and cause severe injury or death. Several of our patients have developed deep-vein thromboses after starting tamoxifen therapy. Symptoms of thrombosis include pain, warmth, and swelling or tenderness

Warning

Women who are taking the anticancer drug tamoxifen also should avoid soy. Tamoxifen works by attaching to estrogen receptors in cancer cells. By doing so, it blocks "real" estrogen or estrogen-like compounds from attaching and thus keeps them from stimulating tumor cell growth. But test tube studies have found that genistein and tamoxifen compete to bind with the estrogen receptors. Usually genistein wins the race, thus negating the desired effects of tamoxifen. For this reason and others, it's prudent for women with estrogen-sensitive breast cancer to avoid and consume no more than four servings of soy foods weekly.

especially in the chest, arm, or leg. Report any such problems to your physician immediately.

ANTITESTOSTERONE AGENTS| Many men taking these drugs de lop a greater sympathy for what women experience during menopause, because they too experience hot flashes. These agents frequently cause impotence, anemia, and a decrease in sexual drive. They can also cause muscle wasting and bone loss.

Oral corticosteroids: The side effects of oral corticosteroids depend on dosage levels and length of time on the medication. The longer you take them, the greater the risk of side effects. The number and severity of side ctfects is a matter of dosage and length of treatment. At lower dosages (less than 10 mg a day), the most common side effects are increased appetite, weight gain, retention of salt and water, and increased susceptibility to infection. These side effects are expected to develop in most people taking corticosteroids.

Long-term use of corticosteroids at higher doses can cause depression and other mental or emotional disturbances in more than half of patients; high blood pressure; diabetes; peptic ulcers; acne; excessive facial hair in women; insomnia; muscle cramps and weakness; thinning and weakening of the skin; osteoporosis; and susceptibility to the formation of blood clots.

WHAT TO DO IF YOU TAKE HORMONES OR ANTIHORMONES |

Breast cancer: Women with breast cancer should follow all the recommendations given in Chapter 4, Special Steps for Preventing Lung, Breast, Prostate, and Colon Cancers, as well as the chemotherapy supplement program given on page 338, including taking lycopene, calcium D-glucarate, indole-3-carbinol, and ground flaxseed.

For women taking tamoxifen, we recommend adding melatonin to the regimen. One study examined the combination of tamoxifen plus melatonin (20 mg a day) in the treatment of metastatic breast cancer that had progressed under treatment with tamoxifen alone 6! Four of the 14 patients had a partial response to this combination: Progression of their disease was delayed by an average of eight months compared with tamoxifen treatment alone. Treatment was well tolerated, and relief of anxiety or depression was also noted by many patients.

There are a number of ways to help reduce or control hot flashes and sweats. Some women find it helpful to avoid or cut down on tea, coffee, nicotine, and alcohol. Interestingly, while black cohosh seems to work in most women, a recent double-blind trial in breast cancer patients found that it did not seem to work.

Tamoxifen also causes severe elevation in blood triglycerides and possibly cholesterol levels as well. Elevation in these blood fats is associated with an increased risk for heart disease. Fortunately, vitamins C and E can help. In one study, supplementation of vitamin C (500 mg daily) and vitamin E (400 mg daily) for 90 days along with tamoxifen (10 mg twice a day) reduced total cholesterol, low-density lipoprotein (LDL) cholesterol. and triglyceride levels while significantly increasing the protective highdensity lipoprotein (HDL) cholesterol level. The authors of the study concluded that these results suggested that tamoxifen treatment is the most effective during co-administration of vitamin C and vitamin E.

Prostate cancer: Men with prostate cancer should follow all the recommendations given in Chapter 4, Special Steps for Preventing Lung, Breast, Prostate, and Colon Cancers, as well as the basic chemotherapy supplement program given in Appendix E (see page 338), including taking lycopene, calcium D-glucarare, indole-3-carbinol, and ground Haxseed. Men taking antihormonal drugs should take extra calcium and should focus on weightbearing and resistance exercise to prevent osteoporosis.

Usually prostate cancer is a slow-growing disease that can be monitored quite easily. That means it's sometimes possible to defer conventional therapy (one term for this strategy is watchful waiting) and try alternative treatments first. If you want to follow this approach, discuss your options with your physicians. Set up a plan for monitoring your condition on a regular basis. In general, we recommend having a PSA test and perhaps a testosterone level test once a month. We also recommend periodic imaging studies, including bone scans, CT scan, or transrectal ultrasound, depending on the stage of your cancer. If the disease appears to be progressing, you and your caregivers can decide on more aggressive strategies.

Microtubule Inhibitor and Chromatin Function Inhibitors

Many of the drugs in this category are derived from plants, including the periwinkle plant (source of the vinca alkaloids vincristine and vin

PC-SPES

PC-SPES is a combination of eight herbs that many men use for treatment or prevention of prostate cancer. (PC stands for prostate cancer," and SPES comes from the Latin word for "hope.") The product was developed by Sophie Chen, a Chinese-born scientist educated in the United States, as a remedy to help a friend with prostate cancer.

Following are the reported ingredients of PC-SPES:

  • Isatis indigotica contains the component indirubin, which is reported to have anticancer activity and has been used in China in the treatment of leukemias.
  • Licorice (Glycyrrhiza glabra and Glycyrrhiza uralensis) contains triterpenoids and flavonoids that might have anticancer effects.
  • Ginseng (Panax ginseng) contains immune-enhancing and anti cancer compounds known as ginsenosides.
  • Reishi mushroom (Ganoderma lucidum) contains polysaccharide molecules (glycans) that have shown significant antitumor effects in test tube studies.
  • Skullcap (Scutellaria baicalensis) contains baicalein, a flavonoid that has shown anticancer properties.
  • Chrysanthemum (Dendranthema morefolium) is a less well-known Chinese herb with unspecified biologic effects.
  • Rabdosia rucescens is thought to contain an antihormonal com pound that has multiple antitumor effects.
  • Saw palmetto (Serenoa repens) has been shown to inhibit the con version of testosterone to its more potent form, dihydrotestosterone. Used primarily as a remedy for benign prostatic hyperplasia (BPH, a noncancerous condition causing prostate enlargement), saw palmetto has been shown to be as effective as conventional drugs in the treatment of mild to moderate cases.

In user surveys, PC-SPES has been found to help about 70 percent of more than 1,700 men with prostate cancer. A study conducted at the University of California at San Francisco found that most prostate cancer patients who have never been treated with hormones will have a significant response to PC-SPES. In the study of the 70 participating subjects, 100 percent had a dedine in their PSA, and 56 percent achieved an undetectable PSA. This effect appears to result primarily from the antihormonal effects of the drug, since more than 80 percent of men taking PC-SPES showed a dramatic decline in their testosterone levels. In some cases the drop was equivalent to castration.

PC-SPES may also have effects against prostate cancer tumors that are not hormone-sensitive. Approximately 60 percent of such patients had significant declines in their PSA. Some of the patients also showed improvements on bone scans and other measures of disease.

PC-SPES can cause side effects. When testosterone levels fall to a certain point, most men develop breast tenderness or breast enlargement, the same side effects seen following treatment with Lupron or DES (diethylsilbesterol). Other side effects include:

  • Decreased libido (sexual desire)
  • Decreased ability to achieve and maintain erections
  • Frequent loose bowel movements or diarrhea (usually mild) in about a third of patients
  • Leg cramps or muscle cramps in about a third of patients
  • Change in urine flow (increase or decrease)
  • Fatigue
  • Allergic reactions
  • Blood clots in legs or lungs (rare)
Our Take on PC-SPES

Even though PC-SPES is a "natural" product, its effects--chat is, reduction in testosterone levels and activity are not. It is an expensive herbal mixture whose active ingredients and mechanism of action are not well defined. We are especially puzzled by reports of dramatic reductions in testosterone levels. Such effects are much larger than are typically seen with most herbal medicines. And PC SPES is not without side effects.

There have been reports from at least two independent laboratories that DES was found in at least two lots of PC-SPES. In February 2002, the FDA issued a warning on PC-SPES, citing that it contained another drug-warfarin (Coumadin), the powerful blood thinner. This report led to a total recall of the product by BotanicLab, the manufacturer. Until these contamination issues of PC-SPES are cleared up, we would recommend avoiding it. Keep an eye on the PSA Rising Web site (www.psa-rising.com) for up-todate information on PC-SPES.

blastine), the Pacific yew tree (paclitaxel), and the May apple (podophyllin derivatives such as etoposide and teniposide). Some of these cellular poisons work by interfering with cellular structures known as microtubules. Microtubules are proteins that control the cell's shape and movement. The major component of microtubules is a protein called tubulin. This molecule contains two subunits, known simply as alpha and beta. Microtubule inhibitors like Taxol and the vinca alkaloids work by disrupting the balance between the alpha and beta units. As a result, they interfere with the physical actions of the cancer cell and disrupt its ability to function and reproduce.

Chromatin inhibitors like etoposide, teniposide, and irinotecan disrupt DNA (chromosome) dynamics. For DNA to carry out a function, part of the long, tightly wound molecule must untwist, change position, and split apart temporarily. That activity is controlled by enzymes known as topoi somerases, which break DNA strands apart and then reseal them. Chromatin inhibitors act by blocking these enzymes. Without those enzymes, the DNA can't do its job and thus the cancer cell can't reproduce.

Paclitaxel and docetaxel are frequently used to treat ovarian cancer, breast cancer, carcinoma of the lung, and head and neck carcinoma. The response rate in these cancers is fairly high. Vincristine, usually in combination with prednisone, is used to induce remission in childhood acute leukemias; complete remissions occur in about 80 to 90 percent of cases. Vincristine is also used for the treatment of Hodgkin's and non-Hodgkin's lymphoma. Combined with bleomycin and cisplatin, vinblastine is very effective in the treatment ot metastatic testicular cancer. The newest of the vinca alkaloids, vindesine shows significant activity in the treatment of acute leukemia, blast crisis of chronic myelogenous leukemia, and Hodgkin's and non-Hodgkin's lymphomas.

Etoposide, often combined with bleomycin and cisplatin, is active against a variety of tumor types, especially resistant testicular tumors. Eroposide plays an important role in the treatment of small-cell lung carcinomas, usually combined with cisplatin. Teniposide appears to be effective for the treatment of acute lymphoblastic leukemia and child hood neuroblastomas, as well as brain tumors in adults. Irinotecan appears to be one of the most active compounds available for the treatment of non-small-cell lung cancer.

TOXICITY AND SIDE EFFECTS| The principal dose-limiting toxicity of these drugs, with the exception of vincristine, is severe bone marrow suppression. Nausea and diarrhea are common but usually are not severe. Mouth sores can be severe at higher doses. Other toxic effects include fever, chills, skin rash, and allergic reactions. Vincristine can cause peripheral nerve damage as well as damage to the nerves that control internal organs. As a result, some patients experience abdominal pain, constipation, urinary retention, and orthostatic hypotension (low blood pressure upon standing). Taxol also causes muscle aches and some reversible neurotoxicities, most often numbness and feelings of pins and needles (paresthesias) in the hands and feet.

WHAT TO DO IF YOU TAKE MICROTUBULE INHIBITORS AND CHROMATIN FUNCTION INHIBITORS |As is the case with all forms of chemotherapy, follow the basic dietary program given above on page 228, as well as those described in Chapter 7, Battling Cancer Through Diet, as well as the basic chemotherapy supplementation program given in Appendix E on page 338. These drugs produce the same sort of side effects as other chemotherapy drugs. The principal dose-limiting toxicity of these drugs (except vincristine) is severe bone marrow suppression. People taking these agents drugs should also take Polyerga (see page 181) and be sure to have at least 40 to 60 mg of whey protein or 3 to 10 g of glutamine daily.

New-Breed Chemotherapy Agents

There are several promising chemotherapy drugs that we call new-breed chemotherapy agents. These drugs have great potential. They are highly selective in their actions, thus doing a better job of targeting cancer cells and leaving normal cells alone. For example, monoclonal antibodies are being developed that recognize specific molecules (called antigens) that appear on only cancer cells. Once attached to the cell, the antibody can inhibit its growth or can act as a "red flag," signaling the immune system to come and destroy the cell. Antibodies are being designed to deliver antitumor drugs, toxins, or radioactive material directly to cancer cells, thus avoiding damage to healthy cells. (You can recognize many of these drugs because their chemical names end with -mab, short for "monoclonal antibody.")

Other new "molecularly targeted" drugs are being developed that bind to specific genetic defects found only in cancer cells.

If you are on one of these new-breed chemotherapy agents, we still believe that it is important to follow the basic dietary program given in Chapter 7, as well as the basic general supplementation program given above.

GLEEVEC |Gleevec (ST1571), used in the treatment of chronic myeloid leukemia (CML), is heralded as the first approved "molecularly targeted" drug. Gleevec treats CML by targeting a specific genetic defect found in cells of patients with this type of cancer. It blocks receptors of a certain enzyme (tyrosine kinase) that leukemic cells depend on to fuel their growth. Because Gleevec's action is so specific, it does not harm normal cells.

The results with Gleevec in CML have been nothing short of miraculous. In April 2001, Brian Druker and colleagues reported the results of a study on Gleevec in the New England Journal of Medicine. Their data showed that Gleevec restored normal blood counts in 53 out of 54 chemotherapy-resistant CML patients, a response rate rarely seen in cancer with a single agent. Fifty-one of these patients were still doing well after a year on the medicine, and most reported few side effects.

While Gleevec is currently approved only for treating CML, studies have shown that it may have potential for the treatment of other cancers that express the specific receptors for tyrosine kinase, including gastrointestinal stromal tumor and small-cell lung cancer. Gleevec's success gives us hope that, in the future, more drugs can be designed to exploit the weaknesses of all types of cancer.

HERCEPTIN| Herceptin (trastuzumab) is a monoclonal antibody developed to specifically seck out a specific antigen known as HER2 receptors that lies on the surface of some cancer cells. About 30 percent of women with breast cancer have multiple copies of a gene, known as HER2, in a single cell. This gene is responsible for producing a protein, HER2 growth factor cell-surface receptor, which plays a role in cell growth and division. Multiple copies of the HER2 gene in a single cell lead to overproduction of the HER2 protein. This causes the cells to grow and divide at an abnormally fast rate. The result: cancer. Breast cancer resulting from HER2 overexpression tends to be very aggressive and resistant to treatment.

In individuals who overexpress the HER2 protein, Herceptin binds to the cell and helps shrink the tumor. Patients are given Herceptin intravenously once a week. Herceptin causes fewer side effects than traditional chemotherapy. The most common adverse reaction to the treatment chills and fever-is usually a response to infusion of the drug and is generally not severe. Herceptin can also cause damage to the heart, however, if so, treatment is discontinued.

RITUXAN |More than 90 percent of people with B-cell type non Hodgkin's lymphoma (NHL) have cancerous white blood cells (Blymphocytes) that express a certain antigen known as CD-20. Rituxan (rituximab) is a monoclonal antibody that binds to CD-20 and destroys the cell. The drug has generated a lot of excitement because of its new way of attacking cancer cells, but it is not cure-all; according to clinical trials, it has a response rate of about 40 to 60 percent. Nor is it free of side effects, but the toxicities from treatment are usually mild and in clude fevers, chills, nausea, rash, and hives. In some cases, severe, even life-threatening, respiratory events have occurred.

Dealing with Hair Loss

For many patients, hair loss is one of the most devastating complications of chemotherapy. Hair loss occurs because treatment with drugs or radiation can kill the cells in the hair follicles. That's because these cells share a trait in common with cancer cells: They reproduce quickly. When the follicles die, the hairs they support fall out.

Some patients experience hair loss and others do not, even when they are taking the same drugs. And not all cancer drugs cause hair loss. Same treatments cause loss of hair from the scalp only, while others cause loss from the scalp and elsewhere on the body. Radiation therapy administered to the head often causes scalp hair loss; in these cases, depending on the radiation dose, the hair may not regrow naturally.

If hair loss does occur, it usually begins within 2 weeks of the start of therapy and gets worse I to 2 months after the start of therapy. In many cases, hair regrowth begins even before therapy is completed. Sometimes the hair that regrows is different in body or texture. In many cases, the next "batch" that grows in is more like the original hair.

Here are some tips for dealing with hair loss:

  • Before hair loss begins, be gentle when brushing and shampooing your hair. Hair loss can be reduced somewhat by avoiding too much brushing or pulling of the hair and by avoiding heat from electric rollers, hair dryers, and curling irons.
  • Before treatment begins or at the very start of treatment, buy a wig or toupee. Doing this before hair loss sets in makes it easier for the wig shop to match your hair color and texture.
  • Be sure to get a prescription from your doctor for the wig, because it is often covered by insurance. Ask your h?alth care team for referrals to wig shops in your area that specialize in dealing with cancer patients.
  • Some women who have long hair go to a salon for a stylish short cut and then have a beautiful wig made from their own hair.
  • If you buy a wig, try on many different ones until you find one that you really like.
  • Consider buying two wigs, one for every day and one for special occasions.
  • Use a sunscreen, sunblock, or hat to protect your scalp from the sun.
  • Wear a hat or scarf outdoors in cold weather to prevent loss of body heat.

New hair growth after chemotherapy or radiation is influenced by age and a wide variety of nutritional and hormonal factors. It is harder for both men and women over the age of 55 years to quickly recover from chemotherapy-induced hair loss. By age 40 or so, the rate of hair growth slows down, and as we continue to age, new hair growth just runs out of steam. New hairs are not replaced as quickly as old ones are lost. Nevertheless, there are things that can be done regardless of age.

In our experience, besides age there are three common causes of fail ure to recover quickly from chemotherapy-induced hair loss (especially in women): (1) other drugs, (2) nutritional deficiencies, and (3) hypothyroidism.

Drug-Induced Hair Loss

There is a long list of drugs that can cause hair loss. Although all the drugs listed in Table 13-3 are capable of causing hair loss, it should not be interpreted that simply because a person is complaining of hair loss and is taking one of these drugs that the drug is the single cause of the hair loss. Of course, for some drugs, most notably chemotherapy agents such as fluorouracil, they are obviously the cause, because they are such powerful inhibitors of hair growth. When medically appropriate, natural alternatives to suspected culprits of hair loss should be employed.

Classes of Drugs That Can Cause Hair Loss

CLASS EXAMPLES
Antibiotics Gentamyacin, chloramphenicol
Anticoagulants Coumadin, heparin
Antidepressants Prozac, desipramine, lithium
Antiepileptics Valproic acid, Dilantin
Cardiovascular drugs ACE inhibitors, beta-blockers
Chemotherapy drugs Adriamycin, vincristine, etoposide
Endocrine drugs Bromocriptine, clomid, danazol
Gout medications Colchicine, allopurinol
Lipid-lowering drugs Gemfibrizol, fenofibrate
Nonsteroidal anti-inflammatory drugs (NSAIDs) Ibuprofen, indomethacin naproxen
Ulcer medications Tagamet, Zantac
Nutritional Deficiencies

A deficiency of any of a number of nutrients can lead to significant hair loss. Deficiencies of zinc, vitamin A, essential fatty acids, and iron are the most common. Typically, in our experience in women with either noticeable hair loss or failure to regrow lost hair after chemotherapy, they will be suffering from apparent deficiencies of all these nutrients, but especially iron. For evaluating iron status, we recommend that you ask your doctor to perform a simple blood test called serum ferritin. When evaluating serum ferritin levels, please be aware that many reference laboratories report low ferritin levels, e.g., 10 to 30 mcg per liter, within the normal range. If the serum ferritin is less than 30 mcg per liter, iron supplementation is indicated at a dosage of 30 mg twice a day between meals (if this recommendation results in abdominal discomfort, take 30 mg with meals three times a day). When serum ferritin levels get below this, hair growth and regeneration are impaired, as the body seeks to conserve the iron.

Hypothyroidism

It is a well-known fact that hair loss is one of the cardinal signs of hypothyroidism. It is estimated that between 1 and 4 percent of the adult population have moderate to severe hypothyroidism, and another 10 to 12 percent have mild hypothyroidism.

Signs and symptoms of hypothyroidism
  • Hair loss
  • Dry, rough skin
  • Course, dry, and brittle hair
  • Thin and brittle nails
  • Depression
  • Weight gain
  • Sensitivity to cold weather
  • Cold hands or feet
  • Elevated cholesterol and triglyceride levels
  • Menstrual abnormalities in women
  • Muscle weakness and joint stiffness
  • Shortness of breath
  • Constipation
  • Low basal body temperature

We make the diagnosis of hypothyroidism by looking at signs and symptoms along with laboratory data. The diagnosis is straightforward when blood measurements of thyroid hormones are clearly abnormal. In milder cases of hypothyroidism, the diagnosis is not as clear. An elevation in thyroid stimulating hormone (TSH) with a normal thyroxine (TP level is generally considered "subclinical," but the accepted normal range for TSH is extremely broad-0.35 to 5.50 uIU per milliliter. We tend to begin thyroid hormone-replacement therapy in patients with TSH values greater than 2.5 uIU per milliliter, especially if they are demonstrating clinical signs of hypothyroidism. If you have signs or symptoms of hypothyroidism, talk to your doctor, as it may require prescription thyroid medication .

Final Comment

Because many cancers can increase the likelihood of forming lifethreatening blood clots, many cancer patients are placed on the anticoagulant drug coumadin (Warfarin). For coumadin to be effective, certain safeguards must be followed. For example, your specific dose of coumadin will be determined according to results of a blood test known as the international normalized ratio (INR).

Your doctor will also counsel you about certain dietary strategies to follow while taking coumadin. You should know, for example, that coumadin works by interfering with vitamin K's role in promoting blood clots. Since green leafy vegetables and green teas contain high levels of vi. tamin K, you should avoid increasing your intake of these foods while taking coumadin. You can eat at the same levels you're accustomed to just don't increase your consumption. Your physician will monitor your blood using the INR test to be sure the coumadin is working and to change your dose (up or down) as needed. The key is consistency: Eat approximately the same-size servings of green leafy vegetables every day.

You may need to adjust your use of other natural remedies if you take coumadin. Here are some guidelines:

  • Co-enzyme Q10 and St. John's wort (Hypericum perforatum) may reduce coumadin's efficacy, while proteolytic enzymes and several herbs, including panax ginseng, devil's claw (Harpagophytum procumbens), and dong quai (Angelica sinensis), can increase its effects. It's likely that you can continue using these products, but don't change the dosage from what your body is accustomed to. INR values must be monitored appropriately.
  • Garlic (Allium sativum) and ginkgo (Ginkgo biloba) extracts may reduce the ability of platelets to stick together, increasing the likelihood of bleeding, but neither appears to interact directly with coumadin. We generally tell patients taking coumadin to avoid these products at higher dosages (more than the equivalent of one clove of garlic a day for garlic or more than 120 mg a day of ginkgo extract) but not to worry if they are just on the typical support dose .
  • Iron, magnesium, and zinc can bind with coumadin, potentially decreasing its absorption and activity. Take coumadin and iron/ magnesium/zinc-containing products at least 2 hours apart.